I. Chapitre and . .. Le,

I. I. Chapitre and . .. La-thérapie-photodynamique,

, Les nanoparticules et la thérapie photodynamique dans le traitement du cancer colorectal

I. .. Chapitre, Les voies d'induction de l'apoptose

V. .. Chapitre,

V. , Les étapes de la macro-autophagie

, Le rôle paradoxal de l'autophagie dans les cancers

V. 4. and .. .. ,

. .. Projet-de-recherche,

. .. Matériels,

I. Chapitre and . .. Expérimentations-in-vitro, Synthèse de la TPPOH libre et des TPPOH-X SNPs

, Dosage du taux cellulaire d'espèces réactives de l'oxygène

I. , Étude de l'internalisation et de la localisation cellulaire

B. Ludovic, , 2019.

I. , Analyses en microscopie électronique à transmission

I. , Analyse de l'expression

I. , 10.2. Analyse multiparamétrique de l'apoptose grâce à l'annexine V et l'iodure de propidium, Analyse quantitative des caspases 3/7 activées

I. I. Chapitre and .. .. Expérimentations-in-vivo, 1. Création d'un modèle de xénogreffe sous-cutanée de cancer colorectal humain, p.126

, Étude de l'efficacité anti-tumorale et de la biocompatibilité

. .. Partie-expérimentale,

I. Chapitre and . .. Expérimentations-in-vitro, 130 I.2. Dosage du taux cellulaire d'espèces réactives de l'oxygène

, Étude de l'internalisation et de la localisation cellulaire des TPPOH-X SNPs par MET

I. , Étude du potentiel membranaire mitochondrial

I. , Analyse quantitative des caspases 3/7 activées

I. .. Adn, Analyse quantitative de la fragmentation de l

I. , Quantification de l'expression d'acteurs de l'autophagie

I. , Analyse de l'autophagie par MET

I. , Étude du niveau d'apoptose après inhibition de l'autophagie

I. , Analyse quantitative des caspases 3/7 activées après inhibition de l'autophagie, p.176

I. , Analyse quantitative de la fragmentation de l'ADN après inhibition de l'autophagie

I. I. Chapitre and . .. Expérimentations-in-vivo,

I. , Étude de la morphologie et de la structure des tumeurs

I. , Étude de la morphologie et de la structure des tumeurs en fin d'étude

I. , Étude de la prolifération des cellules tumorales en fin d'étude

. .. Discussion, 194 I.1. Intérêt de la vectorisation de la TPPOH par des SNPs

, Références bibliographiques 1. Le cancer du côlon : points clés -Cancer du côlon

, Cancer today -Centre international de recherche sur le cancer, 2019.

M. K. Gospodarowicz, C. Wittekind, and D. Brierley, TNM classification des tumeurs malignes, 2019.

, Colon Cancer Treatment (PDQ®): Health Professional Version. PDQ Adult Treatment Editorial Board. Bethesda (MD): National Cancer Institute (US), 2002.

O. Référentiel-côlon, , 2019.

T. Matsuda, K. Yamashita, H. Hasegawa, T. Oshikiri, M. Hosono et al., Recent updates in the surgical treatment of colorectal cancer, Ann Gastroenterol Surg, vol.2018, issue.2, pp.129-165

B. M. Wolpin and R. J. Mayer, Systemic Treatment of Colorectal Cancer, Gastroenterology, vol.134, issue.5, pp.1296-310, 2008.

A. Belliere, O. Chapet, R. Coquard, P. Romestaing, J. M. Ardiet et al., Brachytherapy in carcinomas of anal canal and rectum: techniques and results

, Cancer Radiother J Soc Francaise Radiother Oncol, vol.7, issue.1, pp.24-32, 2003.

S. Myint, A. Smith, F. M. Gollins, S. W. Wong, H. Rao et al., Dose escalation using contact X-ray brachytherapy (Papillon) for rectal cancer: does it improve the chance of organ preservation?, Br J Radiol, vol.90, p.20170175, 1080.

Y. T. Lee, Y. J. Tan, and C. E. Oon, Molecular targeted therapy: Treating cancer with specificity

, Eur J Pharmacol, vol.834, pp.188-96, 2018.

V. J. Verwaal, S. Van-ruth, E. De-bree, G. W. Van-sloothen, H. Van-tinteren et al., Randomized trial of cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy and palliative surgery in patients with peritoneal carcinomatosis of colorectal cancer, J Clin Oncol Off J Am Soc Clin Oncol, vol.21, issue.20, pp.3737-3780, 2003.

D. Elias, J. H. Lefevre, J. Chevalier, A. Brouquet, F. Marchal et al., Complete cytoreductive surgery plus intraperitoneal chemohyperthermia with oxaliplatin for peritoneal carcinomatosis of colorectal origin, J Clin Oncol Off J Am Soc Clin Oncol, vol.27, issue.5, pp.681-686, 2009.
URL : https://hal.archives-ouvertes.fr/hal-00378784

D. Elias, M. Bonnay, J. M. Puizillou, S. Antoun, S. Demirdjian et al., Heated intraoperative intraperitoneal oxaliplatin after complete resection of peritoneal carcinomatosis: pharmacokinetics and tissue distribution, Ann Oncol Off J Eur Soc Med Oncol, vol.13, issue.2, pp.267-72, 2002.

D. Elias, D. Goere, F. Blot, V. Billard, M. Pocard et al., Optimization of hyperthermic intraperitoneal chemotherapy with oxaliplatin plus irinotecan at 43 degrees C after compete cytoreductive surgery: mortality and morbidity in 106 consecutive patients, Ann Surg Oncol, vol.14, issue.6, pp.1818-1842, 2007.

S. Dagois, M. Grienay, M. Pocard, É. Gayat, L. Dico et al., La chimiothérapie hyperthermique intra-péritonéale (CHIP) (podcast), vol.19, pp.308-322, 2015.

N. Kuchen, T. Cereser, S. Hailemariam, and O. Schoeb, Safety and efficacy of pressurized intraperitoneal/intrathoracic aerosol chemotherapy (PIPAC/PITAC) in patients with peritoneal and/or pleural carcinomatosis: A preliminary experience, J Med Ther, vol.2, issue.1, pp.1-6, 2018.

K. Van-der-jeught, H. Xu, Y. Li, X. Lu, and J. G. , Drug resistance and new therapies in colorectal cancer, World J Gastroenterol, vol.24, issue.34, pp.3834-3882, 2018.

M. R. Hamblin and P. Mroz, Advances in Photodynamic Therapy: Basic, Translational and Clinical. 1 edition, 2008.

S. Kwiatkowski, B. Knap, D. Przystupski, J. Saczko, E. K?dzierska et al., Photodynamic therapy -mechanisms, photosensitizers and combinations, Biomed Pharmacother, vol.106, pp.1098-107, 2018.

P. Jichlinski, M. Forrer, J. Mizeret, T. Glanzmann, D. Braichotte et al., Clinical evaluation of a method for detecting superficial surgical transitional cell carcinoma of the bladder by light-induced fluorescence of protoporphyrin IX following the topical application of 5-aminolevulinic acid: preliminary results, Lasers Surg Med, vol.20, issue.4, pp.402-410, 1997.

M. J. Colditz and R. L. Jeffree, Aminolevulinic acid (ALA)-protoporphyrin IX fluorescence guided tumour resection. Part 1: Clinical, radiological and pathological studies, J Clin Neurosci Off J Neurosurg Soc Australas, vol.19, issue.11, pp.1471-1475, 2012.

F. Acerbi, M. Broggi, M. Eoli, E. Anghileri, C. Cavallo et al., Is fluoresceinguided technique able to help in resection of high-grade gliomas? Neurosurg Focus, vol.36, p.5, 2014.

T. B. Manny, A. S. Pompeo, and A. K. Hemal, Robotic partial adrenalectomy using indocyanine green dye with near-infrared imaging: the initial clinical experience, Urology, vol.82, issue.3, pp.738-780, 2013.

Q. Tummers, F. Verbeek, B. E. Schaafsma, M. C. Boonstra, J. R. Van-der-vorst et al., Real-time intraoperative detection of breast cancer using near-infrared fluorescence imaging and Methylene Blue, 25. van der Vorst JR, vol.40, pp.853-861, 2014.

F. Aydogan, V. Ozben, E. Aytac, H. Yilmaz, A. Cercel et al., Excision of Nonpalpable Breast Cancer with Indocyanine Green Fluorescence-Guided Occult Lesion Localization (IFOLL), vol.7, pp.48-51, 2012.

M. Triesscheijn, P. Baas, J. Schellens, and F. A. Stewart, Photodynamic therapy in oncology, The Oncologist, vol.11, issue.9, pp.1034-1078, 2006.

J. Webber, D. Kessel, and D. Fromm, Side effects and photosensitization of human tissues after aminolevulinic acid, J Surg Res, vol.68, issue.1, pp.31-38, 1997.

D. Dolmans, D. Fukumura, and R. K. Jain, Photodynamic therapy for cancer, Nat Rev Cancer, vol.3, issue.5, pp.380-387, 2003.

M. C. Derosa and R. J. Crutchley, Photosensitized singlet oxygen and its applications, Coord Chem Rev, pp.351-71, 2002.

C. S. Foote, Definition of type I and type II photosensitized oxidation, Photochem Photobiol, vol.54, issue.5, p.659, 1991.

M. J. Kulig and L. L. Smith, Sterol metabolism. XXV. Cholesterol oxidation by singlet molecular oxygen, J Org Chem, vol.38, issue.20, pp.3639-3681, 1973.

S. Baptista-m-da, J. Cadet, D. Mascio, P. Ghogare, A. A. Greer et al., Type I and II Photosensitized Oxidation Reactions: Guidelines and Mechanistic Pathways, Photochem Photobiol, vol.93, issue.4, pp.912-921, 2017.

N. L. Oleinick, R. L. Morris, and I. Belichenko, The role of apoptosis in response to photodynamic therapy: what, where, why, and how, Photochem Photobiol Sci Off J Eur Photochem Assoc Eur Soc Photobiol, vol.1, issue.1, pp.1-21, 2002.

R. W. Redmond and I. E. Kochevar, Spatially resolved cellular responses to singlet oxygen, Photochem Photobiol, vol.82, issue.5, pp.1178-86, 2006.

S. Bagdonas, L. W. Ma, V. Iani, R. Rotomskis, P. Juzenas et al., Phototransformations of 5-aminolevulinic acid-induced protoporphyrin IX in vitro: a spectroscopic study, Photochem Photobiol, vol.72, issue.2, pp.186-92, 2000.

J. D. Spikes, Quantum yields and kinetics of the photobleaching of hematoporphyrin, Photofrin II, tetra(4-sulfonatophenyl)-porphine and uroporphyrin, Photochem Photobiol, vol.55, issue.6, pp.797-808, 1992.

H. Abrahamse and M. R. Hamblin, New photosensitizers for photodynamic therapy, Biochem J, vol.2016, issue.4, pp.347-64

P. Agostinis, A. Vantieghem, W. Merlevede, and P. De-witte, Hypericin in cancer treatment: more light on the way, Int J Biochem Cell Biol, vol.34, issue.3, pp.221-262, 2002.

K. M. Lm-davids, The Anticancer Activity of Hypericin in Photodynamic Therapy, J Bioanal Biomed, p.6, 2012.

D. Gabrielli, E. Belisle, D. Severino, A. J. Kowaltowski, and M. S. Baptista, Binding, aggregation and photochemical properties of methylene blue in mitochondrial suspensions, Photochem Photobiol, vol.79, issue.3, pp.227-259, 2004.

J. P. Tardivo, D. Giglio, A. De-oliveira, C. S. Gabrielli, D. S. Junqueira et al., Methylene blue in photodynamic therapy: From basic mechanisms to clinical applications, Photodiagnosis Photodyn Ther, vol.2, issue.3, pp.175-91, 2005.

J. L. Morrill, H. S. Diehl, W. P. Maloney, and N. Gault, University of Minnesota Medical Bulletin

R. L. Lipson, E. J. Baldes, and A. M. Olsen, The use of a derivative of hematoporhyrin in tumor detection, J Natl Cancer Inst, vol.26, pp.1-11, 1961.

R. L. Lipson, E. J. Baldes, and M. J. Gray, Hematoporphyrin derivative for detection and management of cancer, Cancer, vol.20, issue.12, pp.2255-2262, 1967.

T. J. Dougherty, W. R. Potter, and K. R. Weishaupt, The structure of the active component of hematoporphyrin derivative, Prog Clin Biol Res, vol.170, pp.301-315, 1984.

J. Usuda, H. Kato, T. Okunaka, K. Furukawa, H. Tsutsui et al., Photodynamic therapy (PDT) for lung cancers, J Thorac Oncol Off Publ Int Assoc Study Lung Cancer, vol.1, issue.5, pp.489-93, 2006.

U. O. Nseyo, J. Dehaven, T. J. Dougherty, W. R. Potter, D. L. Merrill et al., Photodynamic therapy (PDT) in the treatment of patients with resistant superficial bladder cancer: a long-term experience, J Clin Laser Med Surg, vol.16, issue.1, pp.61-69, 1998.

T. Sutedja, P. Baas, F. Stewart, and N. Van-zandwijk, A pilot study of photodynamic therapy in patients with inoperable non-small cell lung cancer, Eur J Cancer Oxf Engl, vol.28, issue.8-9, pp.1370-1373, 1990.

E. S. Nyman and P. H. Hynninen, Research advances in the use of tetrapyrrolic photosensitizers for photodynamic therapy, J Photochem Photobiol B, vol.73, issue.1-2, pp.1-28, 2004.

P. Lou, L. Jones, and C. Hopper, Clinical outcomes of photodynamic therapy for head-andneck cancer, Technol Cancer Res Treat, vol.2, issue.4, pp.311-318, 2003.

J. F. Savary, P. Monnier, C. Fontolliet, J. Mizeret, G. Wagnières et al., Photodynamic therapy for early squamous cell carcinomas of the esophagus, bronchi, and mouth with m-tetra (hydroxyphenyl) chlorin, Arch Otolaryngol Head Neck Surg, vol.123, issue.2, pp.162-170, 1997.

M. P. Copper, I. B. Tan, H. Oppelaar, M. C. Ruevekamp, and F. A. Stewart, Metatetra(hydroxyphenyl)chlorin photodynamic therapy in early-stage squamous cell carcinoma of the head and neck, Arch Otolaryngol Head Neck Surg, vol.129, issue.7, pp.709-720, 2003.

P. Wyss, V. Schwarz, D. Dobler-girdziunaite, R. Hornung, H. Walt et al., Photodynamic therapy of locoregional breast cancer recurrences using a chlorin-type photosensitizer, Int J Cancer, vol.93, issue.5, pp.720-724, 2001.

S. G. Bown, A. Z. Rogowska, D. E. Whitelaw, W. R. Lees, L. B. Lovat et al., Photodynamic therapy for cancer of the pancreas, Gut, vol.50, issue.4, pp.549-57, 2002.

T. R. Nathan, D. E. Whitelaw, S. C. Chang, W. R. Lees, P. M. Ripley et al., Photodynamic therapy for prostate cancer recurrence after radiotherapy: a phase I study, J Urol, vol.168, issue.4, pp.1427-1459, 2002.

M. F. Renschler, A. R. Yuen, T. J. Panella, M. Tjw, S. Dougherty et al., Photodynamic therapy trials with lutetium texaphyrin (Lu-Tex) in patients with locally recurrent breast cancer, Optical Methods for Tumor Treatment and Detections: Mechanisms and Techniques in Photodynamic Therapy VII, vol.3247, 1998.

H. Patel, R. Mick, J. Finlay, T. C. Zhu, E. Rickter et al., Motexafin lutetiumphotodynamic therapy of prostate cancer: short-and long-term effects on prostatespecific antigen, Clin Cancer Res Off J Am Assoc Cancer Res, vol.14, issue.15, pp.4869-76, 2008.

J. A. Rodriguez-rivera, R. Rodriguez-lay, L. Zegarra-montes, F. Benzaghou, B. Gaillac et al., Expanding indication of padeliporfin (WST11) vascular-targeted photodynamic therapy: results of prostate cancer Latin-American multicenter study

, Actas Urol Esp, vol.42, issue.10, pp.632-640, 2018.

A. Azzouzi, S. Vincendeau, B. E. Cicco, A. Kleinclauss, F. Van-der-poel et al., Padeliporfin vascular-targeted photodynamic therapy versus active surveillance in men with low-risk prostate cancer (CLIN1001 PCM301): an open-label, phase 3, randomised controlled trial, Lancet Oncol, vol.18, issue.2, pp.181-91, 2017.
URL : https://hal.archives-ouvertes.fr/hal-01484971

H. Kato, K. Furukawa, M. Sato, T. Okunaka, Y. Kusunoki et al., Phase II clinical study of photodynamic therapy using mono-L-aspartyl chlorin e6 and diode laser for early superficial squamous cell carcinoma of the lung, Lung Cancer Amst Neth, vol.42, issue.1, pp.103-114, 2003.

T. Yano, H. Kasai, T. Horimatsu, K. Yoshimura, S. Teramukai et al., A multicenter phase II study of salvage photodynamic therapy using talaporfin sodium (ME2906) and a diode laser (PNL6405EPG) for local failure after chemoradiotherapy or radiotherapy for esophageal cancer, Oncotarget, vol.2017, issue.13, pp.22135-22179

, Licence CC BY

M. Kujundzi?, T. J. Vogl, D. Stimac, N. Rustemovi?, R. A. Hsi et al., A Phase II safety and effect on time to tumor progression study of intratumoral light infusion technology using talaporfin sodium in patients with metastatic colorectal cancer, J Surg Oncol, vol.96, issue.6, pp.518-542, 2007.

M. Wachowska, A. Muchowicz, M. Firczuk, M. Gabrysiak, M. Winiarska et al., Aminolevulinic Acid (ALA) as a Prodrug in Photodynamic Therapy of Cancer, Molecules, vol.16, issue.5, pp.4140-64, 2011.

Y. Ohgari, Y. Nakayasu, S. Kitajima, M. Sawamoto, H. Mori et al., Mechanisms involved in delta-aminolevulinic acid (ALA)-induced photosensitivity of tumor cells: relation of ferrochelatase and uptake of ALA to the accumulation of protoporphyrin, Biochem Pharmacol, vol.71, issue.1-2, pp.42-51, 2005.

D. L. Stout and F. F. Becker, Heme synthesis in normal mouse liver and mouse liver tumors, Cancer Res, vol.50, issue.8, pp.2337-2377, 1990.

H. A. Kurwa, S. A. Yong-gee, P. T. Seed, A. C. Markey, and R. J. Barlow, A randomized paired comparison of photodynamic therapy and topical 5-fluorouracil in the treatment of actinic keratoses, J Am Acad Dermatol, vol.41, issue.3, pp.414-422, 1999.

N. Swamy, D. A. James, S. C. Mohr, R. N. Hanson, and R. Ray, An estradiol-porphyrin conjugate selectively localizes into estrogen receptor-positive breast cancer cells, Bioorg Med Chem, vol.10, issue.10, pp.3237-3280, 2002.

N. Parker, M. J. Turk, E. Westrick, J. D. Lewis, P. S. Low et al., Folate receptor expression in carcinomas and normal tissues determined by a quantitative radioligand binding assay, Anal Biochem, vol.338, issue.2, pp.284-93, 2005.

R. Schneider, F. Schmitt, C. Frochot, Y. Fort, N. Lourette et al., Design, synthesis, and biological evaluation of folic acid targeted tetraphenylporphyrin as novel photosensitizers for selective photodynamic therapy, Bioorg Med Chem, vol.13, issue.8, pp.2799-808, 2005.
URL : https://hal.archives-ouvertes.fr/hal-00200165

J. L. Holley, A. Mather, R. T. Wheelhouse, P. M. Cullis, J. A. Hartley et al., Analysis of the in vitro and in vivo effects of Photodynamic Therapy on Prostate Cancer by using new photosensitizers, protoporphyrin IX-polyamine derivatives, Biochim Biophys Acta, vol.52, issue.15, pp.1676-1690, 1992.

M. Lupu, P. Maillard, J. Mispelter, F. Poyer, and C. D. Thomas, A glycoporphyrin story: from chemistry to PDT treatment of cancer mouse models, Photochem Photobiol Sci Off J Eur Photochem Assoc Eur Soc Photobiol, vol.17, issue.11, pp.1599-611, 2018.

C. L. Conway, I. Walker, A. Bell, D. Roberts, S. B. Brown et al., In vivo and in vitro characterisation of a protoporphyrin IX-cyclic RGD peptide conjugate for use in photodynamic therapy, Photochem Photobiol Sci Off J Eur Photochem Assoc Eur Soc Photobiol, vol.7, issue.3, pp.290-298, 2008.

T. Nagaya, K. Sato, T. Harada, Y. Nakamura, P. L. Choyke et al., Near Infrared Photoimmunotherapy Targeting EGFR Positive Triple Negative Breast Cancer: Optimizing the Conjugate-Light Regimen, PloS One, vol.10, issue.8, p.136829, 2015.

K. S. Kim, J. Kim, D. H. Kim, H. S. Hwang, and K. Na, Multifunctional trastuzumab-chlorin e6 conjugate for the treatment of HER2-positive human breast cancer, Biomater Sci, vol.6, issue.5, pp.1217-1243, 2018.

L. Herrera-ornelas, N. J. Petrelli, A. Mittelman, T. J. Dougherty, and D. G. Boyle, Photodynamic therapy in patients with colorectal cancer, Cancer, vol.57, issue.3, pp.677-84, 1986.

T. Patrice, M. T. Foultier, S. Yactayo, F. Adam, J. P. Galmiche et al., Endoscopic photodynamic therapy with hematoporphyrin derivative for primary treatment of gastrointestinal neoplasms in inoperable patients, Dig Dis Sci, vol.35, issue.5, pp.545-52, 1990.

N. Krasner, Laser therapy in the management of benign and malignant tumours in the colon and rectum, Int J Colorectal Dis, vol.4, issue.1, pp.2-5, 1989.

H. Kashtan, M. Z. Papa, B. C. Wilson, A. A. Deutch, and H. S. Stern, Use of photodynamic therapy in the palliation of massive advanced rectal cancer. Phase I/II study, Dis Colon Rectum, vol.34, issue.7, pp.600-604, 1991.

, A Study of Neoadjuvant Photodynamic Immunomodulation for Colon Cancer

C. S. Loh, P. Bliss, S. G. Bown, and N. Krasner, Photodynamic therapy for villous adenomas of the colon and rectum, Endoscopy, vol.26, issue.2, pp.243-249, 1994.

C. S. Loh, A. J. Macrobert, J. Bedwell, J. Regula, N. Krasner et al., Oral versus intravenous administration of 5-aminolaevulinic acid for photodynamic therapy, Br J Cancer, vol.68, issue.1, pp.41-51, 1993.

C. C. Licence, A. By-nc-nd-;-kawczyk-krupka, A. M. Bugaj, W. Latos, K. Zaremba et al., Photodynamic therapy in colorectal cancer treatment: the state of the art in clinical trials, Photodiagnosis Photodyn Ther, vol.94, issue.3, pp.545-53, 2015.

K. Strebhardt and U. A. Paul, Ehrlich's magic bullet concept: 100 years of progress, Nat Rev Cancer, vol.8, issue.6, pp.473-80, 2008.

J. Kreuter, Nanoparticles--a historical perspective, Int J Pharm, vol.331, issue.1, pp.1-10, 2007.

S. Bonvalot, P. L. Rutkowski, J. Thariat, S. Carrère, A. Ducassou et al., NBTXR3, a first-in-class radioenhancer hafnium oxide nanoparticle, plus radiotherapy versus radiotherapy alone in patients with locally advanced soft-tissue sarcoma (Act.In.Sarc): a multicentre, phase 2-3, randomised, controlled trial, Lancet Oncol, vol.20, issue.8, pp.1148-59, 2019.

J. B. Vines, J. Yoon, N. Ryu, D. Lim, and H. Park, Gold Nanoparticles for Photothermal Cancer Therapy. Front Chem, vol.7, p.167, 2019.

M. I. Khot, H. Andrew, H. S. Svavarsdottir, G. Armstrong, A. J. Quyn et al., A Review on the Scope of Photothermal Therapy-Based Nanomedicines in Preclinical Models of Colorectal Cancer, Clin Colorectal Cancer, vol.18, issue.2, pp.200-209, 2019.

N. Bertrand, J. Wu, X. Xu, N. Kamaly, and O. C. Farokhzad, Cancer nanotechnology: the impact of passive and active targeting in the era of modern cancer biology, Adv Drug Deliv Rev, vol.66, pp.2-25, 2014.

R. Duncan and R. Gaspar, Nanomedicine(s) under the microscope, Mol Pharm, vol.8, issue.6, pp.2101-2142, 2011.

H. Hashizume, P. Baluk, S. Morikawa, J. W. Mclean, G. Thurston et al., Openings between defective endothelial cells explain tumor vessel leakiness, Am J Pathol, vol.156, issue.4, pp.1363-80, 2000.

T. P. Padera, B. R. Stoll, J. B. Tooredman, D. Capen, E. Di-tomaso et al., Pathology: cancer cells compress intratumour vessels, Nature, vol.427, issue.6976, p.695, 2004.

H. Kobayashi, R. Watanabe, and P. L. Choyke, Improving conventional enhanced permeability and retention (EPR) effects; what is the appropriate target? Theranostics, vol.4, 2013.

Y. Matsumura and H. Maeda, A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs, Cancer Res, vol.46, pp.6387-92, 1986.

A. K. Iyer, G. Khaled, J. Fang, and H. Maeda, Exploiting the enhanced permeability and retention effect for tumor targeting, Drug Discov Today, vol.11, issue.17, pp.812-820, 2006.

D. Peer, J. M. Karp, S. Hong, O. C. Farokhzad, R. Margalit et al., Nanocarriers as an emerging platform for cancer therapy, Nat Nanotechnol, vol.2, issue.12, pp.751-60, 2007.

A. D. Bangham and R. W. Horne, Negative staining of phospholipids and their structural modification by surface-active agents as observed in the electron microscope, J Mol Biol, vol.8, issue.5, pp.660-670, 1964.

S. D. Steichen, M. Caldorera-moore, and N. A. Peppas, A review of current nanoparticle and targeting moieties for the delivery of cancer therapeutics, Eur J Pharm Sci Off J Eur Fed Pharm Sci, vol.2013, issue.3, pp.416-443

O. M. Koo, I. Rubinstein, and H. Onyuksel, Role of nanotechnology in targeted drug delivery and imaging: a concise review, Nanomedicine Nanotechnol Biol Med, vol.1, issue.3, pp.193-212, 2005.

P. Couvreur, B. Kante, M. Roland, and P. Speiser, Adsorption of Antineoplastic Drugs to Polyalkylcyanoacrylate Nanoparticles and Their Release in Calf Serum, J Pharm Sci, vol.68, issue.12, pp.1521-1525, 1979.

P. Couvreur, B. Kante, L. Grislain, M. Roland, and P. Speiser, Toxicity of Polyalkylcyanoacrylate Nanoparticles II: Doxorubicin-Loaded Nanoparticles, J Pharm Sci, vol.71, issue.7, pp.790-792, 1982.

S. Mura, E. Fattal, and J. Nicolas, From poly(alkyl cyanoacrylate) to squalene as core material for the design of nanomedicines, J Drug Target, vol.27, issue.5-6, pp.470-501, 2019.

E. C. Gryparis, M. Hatziapostolou, E. Papadimitriou, and K. Avgoustakis, Anticancer activity of cisplatin-loaded PLGA-mPEG nanoparticles on LNCaP prostate cancer cells, Eur J Pharm Biopharm Off J Arbeitsgemeinschaft Pharm Verfahrenstechnik EV, vol.67, issue.1, pp.1-8, 2007.

A. Caminade and C. Turrin, Dendrimers for drug delivery, J Mater Chem B, vol.2014, issue.26, pp.4055-66
URL : https://hal.archives-ouvertes.fr/hal-02007939

P. He, S. S. Davis, and L. Illum, In vitro evaluation of the mucoadhesive properties of chitosan microspheres, Int J Pharm, vol.166, issue.1, pp.75-88, 1998.

S. Mitra, U. Gaur, P. C. Ghosh, and A. N. Maitra, Tumour targeted delivery of encapsulated dextran-doxorubicin conjugate using chitosan nanoparticles as carrier, J Control Release Off J Control Release Soc, vol.74, issue.1-3, pp.317-340, 2001.

J. H. Maeng, D. Lee, K. H. Jung, Y. Bae, I. Park et al., Multifunctional doxorubicin loaded superparamagnetic iron oxide nanoparticles for chemotherapy and magnetic resonance imaging in liver cancer, Biomaterials, issue.18, pp.4995-5006, 2010.

S. M. Dadfar, K. Roemhild, N. I. Drude, V. Stillfried, S. Knüchel et al., Iron oxide nanoparticles: Diagnostic, therapeutic and theranostic applications, Adv Drug Deliv Rev, vol.138, pp.302-327, 2019.

C. Martinelli, C. Pucci, and G. Ciofani, Nanostructured carriers as innovative tools for cancer diagnosis and therapy, APL Bioeng, vol.2019, issue.1, p.11502

K. Mahmoudi, A. Bouras, D. Bozec, R. Ivkov, and C. Hadjipanayis, Magnetic hyperthermia therapy for the treatment of glioblastoma: a review of the therapy's history, efficacy and application in humans, Int J Hyperth Off J Eur Soc Hyperthermic Oncol North Am Hyperth Group, vol.34, issue.8, pp.1316-1344, 2018.

K. Black, Y. Wang, H. P. Luehmann, X. Cai, W. Xing et al., Radioactive 198Au-doped nanostructures with different shapes for in vivo analyses of their biodistribution, tumor uptake, and intratumoral distribution, ACS Nano, vol.8, issue.5, pp.4385-94, 2014.

J. Guo, K. Rahme, Y. He, L. Li, J. D. Holmes et al., Gold nanoparticles enlighten the future of cancer theranostics, Int J Nanomedicine, vol.12, pp.6131-52, 2017.

R. Chen, X. Wang, X. Yao, X. Zheng, J. Wang et al., Near-IR-triggered photothermal/photodynamic dual-modality therapy system via chitosan hybrid nanospheres, Biomaterials, vol.34, issue.33, pp.8314-8336, 2013.

Y. Chen, Y. Gao, H. Chen, D. Zeng, Y. Li et al., Engineering Inorganic Nanoemulsions/Nanoliposomes by Fluoride-Silica Chemistry for Efficient Delivery/Co-Delivery of Hydrophobic Agents, Adv Funct Mater, vol.22, issue.8, pp.1586-97, 2012.

L. Huang, J. Ma, X. Wang, P. Zhang, L. Yu et al., Mesoporous silica nanoparticlesloaded methyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl) propanoate as a smart antioxidant of synthetic ester oil, Tribol Int, vol.121, pp.114-134, 2018.

. Silica-coated-gold and . Nanoparticles, Surface Chemistry, Properties, Benefits and Applications

M. Vallet-regi, A. Rámila, R. P. Del-real, and J. Pérez-pariente, A New Property of MCM-41: Drug Delivery System, Chem Mater, vol.13, issue.2, pp.308-319, 2001.

X. Wu, M. Wu, X. Zhao, and J. , Recent Development of Silica Nanoparticles as Delivery Vectors for Cancer Imaging and Therapy, Nanomedicine Nanotechnol Biol Med, vol.10, issue.2, pp.297-312, 2014.

Y. Yang and C. Yu, Advances in silica based nanoparticles for targeted cancer therapy, Nanomedicine Nanotechnol Biol Med, vol.12, issue.2, pp.317-349, 2016.

. Hong-s-ho and Y. Choi, Mesoporous silica-based nanoplatforms for the delivery of photodynamic therapy agents, J Pharm Investig, vol.48, issue.1, pp.3-17, 2018.

J. Lu, M. Liong, Z. Li, J. I. Zink, F. Tamanoi et al., Biodistribution, and Drug-Delivery Efficiency of Mesoporous Silica Nanoparticles for Cancer Therapy in Animals, Small, vol.6, issue.16, pp.1794-805, 2010.

I. Roy, T. Y. Ohulchanskyy, H. E. Pudavar, E. J. Bergey, A. R. Oseroff et al., Ceramic-based nanoparticles entrapping water-insoluble photosensitizing anticancer drugs: a novel drug-carrier system for photodynamic therapy, J Am Chem Soc, vol.125, issue.26, pp.7860-7865, 2003.

X. He, X. Wu, K. Wang, B. Shi, and L. Hai, Methylene blue-encapsulated phosphonateterminated silica nanoparticles for simultaneous in vivo imaging and photodynamic therapy, Biomaterials, vol.30, issue.29, pp.5601-5610, 2009.

M. Gary-bobo, O. Hocine, D. Brevet, M. Maynadier, L. Raehm et al., Cancer therapy improvement with mesoporous silica nanoparticles combining targeting, drug delivery and PDT, Int J Pharm, vol.423, issue.2, pp.509-524, 2012.
URL : https://hal.archives-ouvertes.fr/hal-00656891

N. Chiannilkulchai, N. Ammoury, B. Caillou, J. P. Devissaguet, and P. Couvreur, Hepatic tissue distribution of doxorubicin-loaded nanoparticles after i.v. administration in reticulosarcoma M 5076 metastasis-bearing mice, Cancer Chemother Pharmacol, vol.26, issue.2, pp.122-128, 1990.

L. Barraud, P. Merle, E. Soma, L. Lefrançois, S. Guerret et al., Increase of doxorubicin sensitivity by doxorubicin-loading into nanoparticles for hepatocellular carcinoma cells in vitro and in vivo, J Hepatol, vol.42, issue.5, pp.736-779, 2005.

S. M. Moghimi, A. C. Hunter, and J. C. Murray, Long-circulating and target-specific nanoparticles: theory to practice, Pharmacol Rev, vol.53, issue.2, pp.283-318, 2001.

S. M. Moghimi and J. Szebeni, Stealth liposomes and long circulating nanoparticles: critical issues in pharmacokinetics, opsonization and protein-binding properties, Prog Lipid Res, vol.42, issue.6, pp.463-78, 2003.

A. A. Gabizon, Stealth liposomes and tumor targeting: one step further in the quest for the magic bullet, Clin Cancer Res Off J Am Assoc Cancer Res, vol.7, issue.2, pp.223-228, 2001.

T. Ishida, R. Maeda, M. Ichihara, K. Irimura, and H. Kiwada, Accelerated clearance of PEGylated liposomes in rats after repeated injections, J Control Release Off J Control Release Soc, vol.88, issue.1, pp.35-42, 2003.

A. Lila, A. S. Kiwada, H. Ishida, and T. , The accelerated blood clearance (ABC) phenomenon: clinical challenge and approaches to manage, J Control Release Off J Control Release Soc, vol.172, issue.1, pp.38-47, 2013.

A. Shrotri, H. Kobayashi, and A. Fukuoka, Chapter Two-Catalytic Conversion of Structural Carbohydrates and Lignin to Chemicals, Adv. Catal, vol.60, pp.59-123, 2017.

J. Ma, D. Li, L. Zhong, F. Du, J. Tan et al., Synthesis and characterization of biofunctional quaternized xylan-Fe2O3 core/shell nanocomposites and modification with polylysine and folic acid, Carbohydr Polym, vol.199, pp.382-391, 2018.

S. Daus and T. Heinze, Xylan-based nanoparticles: prodrugs for ibuprofen release, Macromol Biosci, vol.10, issue.2, pp.211-231, 2010.

. Sauraj, V. Kumar, B. Kumar, F. Deeba, S. Bano et al., Lipophilic 5-fluorouracil prodrug encapsulated xylan-stearic acid conjugates nanoparticles for colon cancer therapy, Int J Biol Macromol, vol.128, pp.204-217, 2019.

. Sauraj, S. U. Kumar, V. Kumar, R. Priyadarshi, P. Gopinath et al., pH-responsive prodrug nanoparticles based on xylan-curcumin conjugate for the efficient delivery of curcumin in cancer therapy, Carbohydr Polym, vol.188, pp.252-261, 2018.

K. M. Mcneeley, E. Karathanasis, A. V. Annapragada, and R. V. Bellamkonda, Masking and triggered unmasking of targeting ligands on nanocarriers to improve drug delivery to brain tumors, Biomaterials, vol.30, pp.3986-95, 2009.

B. Stella, S. Arpicco, M. T. Peracchia, D. Desmaële, J. Hoebeke et al., Design of folic acid-conjugated nanoparticles for drug targeting, J Pharm Sci, vol.89, issue.11, pp.1452-64, 2000.

J. E. Schroeder, I. Shweky, H. Shmeeda, U. Banin, and A. Gabizon, Folate-mediated tumor cell uptake of quantum dots entrapped in lipid nanoparticles, J Control Release Off J Control Release Soc, vol.124, issue.1-2, pp.28-34, 2007.

R. Van-der-meel, L. Vehmeijer, R. J. Kok, G. Storm, and E. Van-gaal, Ligand-targeted particulate nanomedicines undergoing clinical evaluation: current status, Adv Drug Deliv Rev, vol.65, issue.10, pp.1284-98, 2013.

J. Shi, P. W. Kantoff, R. Wooster, and O. C. Farokhzad, Cancer nanomedicine: progress, challenges and opportunities, Nat Rev Cancer, vol.17, issue.1, pp.20-37, 2017.

C. L. Ventola, Progress in Nanomedicine: Approved and Investigational Nanodrugs. Pharm Ther, vol.42, pp.742-55, 2017.

, Phase II Study of Combined Temozolomide and SGT-53 for Treatment of Recurrent Glioblastoma. Identifier: NCT02340156

, Study of PNT2258 for Treatment of Relapsed or Refractory Non-Hodgkin's Lymphoma. Identifier: NCT01733238

, Chemotherapy of Physician's Choice Plus Trastuzumab in HER2-Positive Locally Advanced/Metastatic Breast Cancer Patients (HERMIONE), MM-302 Plus Trastuzumab vs

, Multicenter Study Of CPX-1 (Irinotecan HCl: Floxuridine) Liposome Injection In Patients With Advanced Colorectal Cancer. Identifier: NCT00361842

K. Nawalany, A. Rusin, M. Kepczy?ski, A. Mikhailov, G. Kramer-marek et al., Comparison of photodynamic efficacy of tetraarylporphyrin pegylated or encapsulated in liposomes: in vitro studies, J Photochem Photobiol B, vol.97, issue.1, pp.8-17, 2009.

V. Simon, C. Devaux, A. Darmon, T. Donnet, E. Thiénot et al., Pp IX silica nanoparticles demonstrate differential interactions with in vitro tumor cell lines and in vivo mouse models of human cancers, Photochem Photobiol, vol.86, issue.1, pp.213-235, 2010.

O. Bourdon, I. Laville, D. Carrez, A. Croisy, P. Fedel et al., Biodistribution of meta-tetra(hydroxyphenyl)chlorin incorporated into surface-modified nanocapsules in tumor-bearing mice, Photochem Photobiol Sci Off J Eur Photochem Assoc Eur Soc Photobiol, vol.1, issue.9, pp.709-723, 2002.

S. J. Lee, H. Koo, H. Jeong, M. S. Huh, Y. Choi et al., Comparative study of photosensitizer loaded and conjugated glycol chitosan nanoparticles for cancer therapy, J Control Release Off J Control Release Soc, vol.152, issue.1, pp.21-30, 2011.

G. Obaid, I. Chambrier, M. J. Cook, and D. A. Russell, Cancer targeting with biomolecules: a comparative study of photodynamic therapy efficacy using antibody or lectin conjugated phthalocyanine-PEG gold nanoparticles, Photochem Photobiol Sci Off J Eur Photochem Assoc Eur Soc Photobiol, vol.14, issue.4, pp.737-784, 2015.

S. M. Abdelghany, D. Schmid, J. Deacon, J. Jaworski, F. Fay et al., Enhanced antitumor activity of the photosensitizer meso-Tetra(N-methyl-4-pyridyl) porphine tetra tosylate through encapsulation in antibody-targeted chitosan/alginate nanoparticles, Biomacromolecules, vol.14, issue.2, pp.302-312, 2013.

C. He, X. Duan, N. Guo, C. Chan, C. Poon et al., Core-shell nanoscale coordination polymers combine chemotherapy and photodynamic therapy to potentiate checkpoint blockade cancer immunotherapy, Nat Commun, vol.7, p.12499, 2016.

J. F. Kerr, A. H. Wyllie, and A. R. Currie, Apoptosis: a basic biological phenomenon with wideranging implications in tissue kinetics, Br J Cancer, vol.26, issue.4, pp.239-57, 1972.

S. Elmore, Apoptosis: a review of programmed cell death, Toxicol Pathol, vol.35, issue.4, pp.495-516, 2007.

B. Conradt, Genetic control of programmed cell death during animal development, Annu Rev Genet, vol.43, pp.493-523, 2009.

J. Massé, T. Watrin, A. Laurent, S. Deschamps, D. Guerrier et al., The developing female genital tract: from genetics to epigenetics, Int J Dev Biol, vol.53, issue.2-3, pp.411-435, 2009.

Y. Fuchs and H. Steller, Programmed cell death in animal development and disease, Cell, vol.147, issue.4, pp.742-58, 2011.

G. Denecker, E. Hoste, B. Gilbert, T. Hochepied, P. Ovaere et al., Caspase-14 protects against epidermal UVB photodamage and water loss, Nat Cell Biol, vol.9, issue.6, pp.666-74, 2007.

S. Shalini, L. Dorstyn, S. Dawar, S. Kumar, and . Old, new and emerging functions of caspases, Cell Death Differ, vol.22, issue.4, pp.526-565, 2015.

A. Couzinet, Z. Hérincs, and A. Hueber, Régulation de la mort cellulaire programmée : vers une conception plus dynamique. médecine/sciences, vol.18, pp.841-52, 2002.

O. Julien and J. A. Wells, Caspases and their substrates, Cell Death Differ, vol.24, issue.8, pp.1380-1389, 2017.

Y. Nakatani, T. Kleffmann, K. Linke, S. M. Condon, M. G. Hinds et al., Regulation of ubiquitin transfer by XIAP, a dimeric RING E3 ligase, Biochem J, vol.450, issue.3, pp.629-667, 2013.

N. Zamzami, P. Marchetti, M. Castedo, D. Decaudin, A. Macho et al., Sequential reduction of mitochondrial transmembrane potential and generation of reactive oxygen species in early programmed cell death, J Exp Med, vol.182, issue.2, pp.367-77, 1995.

A. Giménez-cassina and N. N. Danial, Regulation of mitochondrial nutrient and energy metabolism by BCL-2 family proteins, Trends Endocrinol Metab TEM, vol.26, issue.4, pp.165-75, 2015.

T. Shibue and T. Taniguchi, BH3-only proteins: integrated control point of apoptosis, Int J Cancer, vol.119, issue.9, pp.2036-2079, 2006.

A. Antignani and R. J. Youle, How do Bax and Bak lead to permeabilization of the outer mitochondrial membrane?, Curr Opin Cell Biol, vol.18, issue.6, pp.685-694, 2006.

I. Marzo, C. Brenner, N. Zamzami, S. A. Susin, G. Beutner et al., The permeability transition pore complex: a target for apoptosis regulation by caspases and bcl-2-related proteins, J Exp Med, vol.187, issue.8, pp.1261-71, 1998.

N. Zamzami and G. Kroemer, The mitochondrion in apoptosis: how Pandora's box opens, Nat Rev Mol Cell Biol, vol.2, issue.1, pp.67-71, 2001.

K. S. Mccommis and C. P. Baines, The Role of VDAC in Cell Death: Friend or Foe?, Biochim Biophys Acta, vol.1818, issue.6, pp.1444-50, 2012.

S. J. Riedl and G. S. Salvesen, The apoptosome: signalling platform of cell death, Nat Rev Mol Cell Biol, vol.8, issue.5, pp.405-418, 2007.

E. Daugas, D. Nochy, L. Ravagnan, M. Loeffler, S. A. Susin et al., Apoptosisinducing factor (AIF): a ubiquitous mitochondrial oxidoreductase involved in apoptosis, FEBS Lett, vol.476, issue.3, pp.118-141, 2000.

L. Y. Li, X. Luo, and X. Wang, Endonuclease G is an apoptotic DNase when released from mitochondria, Nature, vol.412, issue.6842, pp.95-104, 2001.

K. Plaetzer, T. Kiesslich, T. Verwanger, and B. Krammer, The Modes of Cell Death Induced by PDT: An Overview, Med Laser Appl, vol.18, issue.1, pp.7-19, 2003.

P. Mroz, A. Yaroslavsky, G. B. Kharkwal, and M. R. Hamblin, Cell Death Pathways in Photodynamic Therapy of Cancer, Cancers, vol.3, issue.2, pp.2516-2555, 2011.

I. E. Furre, S. Shahzidi, Z. Luksiene, M. Møller, E. Borgen et al., Targeting PBR by hexaminolevulinate-mediated photodynamic therapy induces apoptosis through translocation of apoptosis-inducing factor in human leukemia cells, Cancer Res, vol.65, issue.23, pp.11051-60, 2005.

M. Lam, N. L. Oleinick, and A. L. Nieminen, Photodynamic therapy-induced apoptosis in epidermoid carcinoma cells. Reactive oxygen species and mitochondrial inner membrane permeabilization, J Biol Chem, vol.276, issue.50, pp.47379-86, 2001.

A. Vantieghem, Y. Xu, W. Declercq, P. Vandenabeele, G. Denecker et al., Different pathways mediate cytochrome c release after photodynamic therapy with hypericin, Photochem Photobiol, vol.74, issue.2, pp.133-175, 2001.

M. Teiten, S. Marchal, D. 'hallewin, M. A. Guillemin, F. Bezdetnaya et al., Primary photodamage sites and mitochondrial events after Foscan photosensitization of MCF-7 human breast cancer cells, Photochem Photobiol, vol.78, issue.1, pp.9-14, 2003.

S. Chiu, L. Xue, J. Usuda, K. Azizuddin, and N. L. Oleinick, Bax is essential for mitochondrion-mediated apoptosis but not for cell death caused by photodynamic therapy, Br J Cancer, vol.89, issue.8, pp.1590-1597, 2003.

P. Ferenc, P. Solár, J. Kleban, J. Mikes, and P. Fedorocko, Down-regulation of Bcl-2 and Akt induced by combination of photoactivated hypericin and genistein in human breast cancer cells, J Photochem Photobiol B, vol.98, issue.1, pp.25-34, 2010.

J. Koval, J. Mikes, R. Jendzelovský, M. Kello, P. Solár et al., Degradation of HER2 receptor through hypericin-mediated photodynamic therapy, Photochem Photobiol, vol.86, issue.1, pp.200-205, 2010.

L. Y. Xue, S. M. Chiu, and N. L. Oleinick, Photochemical destruction of the Bcl-2 oncoprotein during photodynamic therapy with the phthalocyanine photosensitizer Pc 4, Oncogene, vol.20, issue.26, pp.3420-3427, 2001.

W. Li, J. Li, and J. Bao, Microautophagy: lesser-known self-eating, Cell Mol Life Sci CMLS, vol.69, issue.7, pp.1125-1161, 2012.

A. E. Majeski and J. F. Dice, Mechanisms of chaperone-mediated autophagy, Int J Biochem Cell Biol, vol.36, issue.12, pp.2435-2479, 2004.

Y. Fujiwara, H. Kikuchi, S. Aizawa, A. Furuta, Y. Hatanaka et al., Direct uptake and degradation of DNA by lysosomes, Autophagy, vol.2013, issue.8, pp.1167-71

Y. Fujiwara, A. Furuta, H. Kikuchi, S. Aizawa, Y. Hatanaka et al., Discovery of a novel type of autophagy targeting RNA, Autophagy, vol.2013, issue.3, pp.403-412

N. Mizushima, A brief history of autophagy from cell biology to physiology and disease, Nat Cell Biol, vol.20, issue.5, pp.521-528, 2018.

D. C. Rubinsztein, T. Shpilka, and Z. Elazar, Mechanisms of autophagosome biogenesis, Curr Biol CB, vol.22, issue.1, pp.29-34, 2012.

N. Mizushima, T. Yoshimori, and Y. Ohsumi, The role of Atg proteins in autophagosome formation, Annu Rev Cell Dev Biol, vol.27, pp.107-139, 2011.

Y. Fu, Z. Huang, L. Hong, J. Lu, D. Feng et al., Targeting ATG4 in Cancer Therapy, Cancers (Basel), vol.2019, issue.5, p.649

D. J. Klionsky, K. Abdelmohsen, A. Abe, M. J. Abedin, H. Abeliovich et al., Guidelines for the use and interpretation of assays for monitoring autophagy, Autophagy, vol.12, issue.1, pp.1-222, 2016.
URL : https://hal.archives-ouvertes.fr/hal-01921322

N. Mizushima, Y. Ohsumi, and T. Yoshimori, Autophagosome formation in mammalian cells, Cell Struct Funct, vol.27, issue.6, pp.421-430, 2002.

T. Hanada, N. N. Noda, Y. Satomi, Y. Ichimura, Y. Fujioka et al., The Atg12-Atg5 conjugate has a novel E3-like activity for protein lipidation in autophagy, J Biol Chem, vol.282, issue.52, pp.37298-302, 2007.

Z. Yu, T. Ni, B. Hong, H. Wang, F. Jiang et al., Dual roles of Atg8-PE deconjugation by Atg4 in autophagy, Autophagy, vol.2012, issue.6, pp.883-92

K. Abounit, T. M. Scarabelli, and R. B. Mccauley, Autophagy in mammalian cells, World J Biol Chem, vol.2012, issue.1, pp.1-6

B. Levine and G. Kroemer, Autophagy in the pathogenesis of disease, Cell, vol.132, issue.1, pp.27-42, 2008.

A. Terman, B. Gustafsson, and U. T. Brunk, Autophagy, organelles and ageing, J Pathol, vol.211, issue.2, pp.134-177, 2007.

S. S. Singh, S. Vats, A. Chia, T. Z. Tan, S. Deng et al., Dual role of autophagy in hallmarks of cancer, Oncogene, vol.37, issue.9, pp.1142-58, 2018.

R. Mathew and E. White, Why sick cells produce tumors: the protective role of autophagy, Autophagy, vol.3, issue.5, pp.502-507, 2007.

A. Takamura, M. Komatsu, T. Hara, A. Sakamoto, C. Kishi et al., Autophagydeficient mice develop multiple liver tumors, Genes Dev, vol.25, issue.8, pp.795-800, 2011.

R. Xie, F. Wang, W. L. Mckeehan, and L. Liu, Autophagy enhanced by microtubule-and mitochondrion-associated MAP1S suppresses genome instability and hepatocarcinogenesis, Cancer Res, vol.71, issue.24, pp.7537-7583, 2011.

R. Mathew, V. Karantza-wadsworth, and E. White, Role of autophagy in cancer, Nat Rev Cancer, vol.7, issue.12, pp.961-968, 2007.

E. Y. Liu and K. M. Ryan, Autophagy and cancer--issues we need to digest, J Cell Sci, vol.2012, pp.2349-58

J. Li, N. Hou, A. Faried, S. Tsutsumi, T. Takeuchi et al., Inhibition of autophagy by 3-MA enhances the effect of 5-FU-induced apoptosis in colon cancer cells, Ann Surg Oncol, vol.16, issue.3, pp.761-71, 2009.

J. Y. Guo, G. Karsli-uzunbas, R. Mathew, S. C. Aisner, J. J. Kamphorst et al., Autophagy suppresses progression of K-ras-induced lung tumors to oncocytomas and maintains lipid homeostasis, Genes Dev, vol.27, issue.13, pp.1447-61, 2013.

H. Wei, S. Wei, B. Gan, X. Peng, W. Zou et al., Suppression of autophagy by FIP200 deletion inhibits mammary tumorigenesis, Genes Dev, vol.25, issue.14, pp.1510-1537, 2011.

R. Lazova, V. Klump, and J. Pawelek, Autophagy in cutaneous malignant melanoma, J Cutan Pathol, vol.37, issue.2, pp.256-68, 2010.

S. Galavotti, S. Bartesaghi, D. Faccenda, M. Shaked-rabi, S. Sanzone et al., The autophagy-associated factors DRAM1 and p62 regulate cell migration and invasion in glioblastoma stem cells, Oncogene, vol.32, issue.6, pp.699-712, 2013.

E. E. Mowers, M. N. Sharifi, and K. F. Macleod, Autophagy in cancer metastasis, Oncogene, vol.2017, issue.12, pp.1619-1649

L. Galluzzi, J. M. Bravo-san-pedro, B. Levine, D. R. Green, and G. Kroemer, Pharmacological modulation of autophagy: therapeutic potential and persisting obstacles, Nat Rev Drug Discov, vol.16, issue.7, pp.487-511, 2017.

J. J. Reiners, P. Agostinis, K. Berg, N. L. Oleinick, and D. Kessel, Assessing autophagy in the context of photodynamic therapy, Autophagy, vol.6, issue.1, pp.7-18, 2010.

R. Scherz-shouval, E. Shvets, E. Fass, H. Shorer, L. Gil et al., Reactive oxygen species are essential for autophagy and specifically regulate the activity of Atg4, EMBO J, vol.26, issue.7, pp.1749-60, 2007.

D. Lihuan, Z. Jingcun, J. Ning, W. Guozeng, C. Yiwei et al., Photodynamic therapy with the novel photosensitizer chlorophyllin f induces apoptosis and autophagy in human bladder cancer cells, Lasers Surg Med, vol.46, issue.4, pp.319-353, 2014.

P. Tu, Q. Huang, Y. Ou, X. Du, K. Li et al., Aloe-emodin-mediated photodynamic therapy induces autophagy and apoptosis in human osteosarcoma cell line MG-63 through the ROS/JNK signaling pathway, Oncol Rep, vol.35, issue.6, pp.3209-3224, 2016.

Q. Xue, X. Wang, P. Wang, K. Zhang, and Q. Liu, Role of p38MAPK in apoptosis and autophagy responses to photodynamic therapy with Chlorin e6, Photodiagnosis Photodyn Ther, vol.12, issue.1, pp.84-91, 2015.

M. Wei, M. Chen, K. Chen, P. Lou, L. Sy-f et al., Autophagy promotes resistance to photodynamic therapy-induced apoptosis selectively in colorectal cancer stem-like cells, Autophagy, vol.10, issue.7, pp.1179-92, 2014.

D. Kessel and N. L. Oleinick, Initiation of Autophagy by Photodynamic Therapy, Methods Enzymol, vol.453, pp.1-16, 2009.

D. Kessel, Subcellular Targets for Photodynamic Therapy: Implications for Initiation of Apoptosis and Autophagy, J Natl Compr Cancer Netw JNCCN, vol.10, issue.2, pp.56-65, 2012.

J. A. Caruso, P. A. Mathieu, A. Joiakim, B. Leeson, D. Kessel et al., Differential susceptibilities of murine hepatoma 1c1c7 and Tao cells to the lysosomal photosensitizer NPe6: influence of aryl hydrocarbon receptor on lysosomal fragility and protease contents, Mol Pharmacol, vol.65, issue.4, pp.1016-1044, 2004.

S. Bouramtane, L. Bretin, A. Pinon, D. Leger, B. Liagre et al., Porphyrin-xylancoated silica nanoparticles for anticancer photodynamic therapy, Carbohydr Polym, vol.213, pp.168-75, 2019.

C. Lepage, D. Y. Léger, J. Bertrand, F. Martin, J. L. Beneytout et al., Diosgenin induces death receptor-5 through activation of p38 pathway and promotes TRAIL-induced apoptosis in colon cancer cells, Cancer Lett, vol.301, issue.2, pp.193-202, 2011.

, Guidance Document on Using In Vitro Data to Estimate In Vivo Starting Doses for Acute Toxicity, pp.1-4500

J. Li, N. Hou, A. Faried, S. Tsutsumi, and H. Kuwano, Inhibition of autophagy augments 5-fluorouracil chemotherapy in human colon cancer in vitro and in vivo model, Eur J Cancer, vol.46, issue.10, pp.1900-1909, 2010.

E. Secret, M. Maynadier, A. Gallud, M. Gary-bobo, A. Chaix et al., Anionic porphyrin-grafted porous silicon nanoparticles for photodynamic therapy, Chem Commun Camb Engl, vol.49, issue.39, pp.4202-4206, 2013.
URL : https://hal.archives-ouvertes.fr/hal-00809285

Z. Youssef, V. Jouan-hureaux, L. Colombeau, P. Arnoux, A. Moussaron et al., Titania and silica nanoparticles coupled to Chlorin e6 for anti-cancer photodynamic therapy, Photodiagnosis Photodyn Ther, vol.22, pp.115-141, 2018.
URL : https://hal.archives-ouvertes.fr/hal-01925410

, Licence CC BY

S. Bharathiraja, M. S. Moorthy, P. Manivasagan, H. Seo, K. D. Lee et al., Chlorin e6 conjugated silica nanoparticles for targeted and effective photodynamic therapy, Photodiagnosis Photodyn Ther, vol.19, pp.212-232, 2017.

I. Brezániová, K. Záruba, J. Králová, A. Sinica, H. Adámková et al., Silica-based nanoparticles are efficient delivery systems for temoporfin, Photodiagnosis Photodyn Ther, vol.21, pp.275-84, 2018.

T. Asefa and Z. Tao, Biocompatibility of Mesoporous Silica Nanoparticles, Chem Res Toxicol, vol.2012, issue.11, pp.2265-84

Y. Shi, M. L. Miller, and A. Pasqua, Biocompatibility of Mesoporous Silica Nanoparticles?, Comments Inorg Chem, vol.2016, issue.2, pp.61-80

S. Hossen, M. K. Hossain, M. K. Basher, M. Mia, M. T. Rahman et al., Smart nanocarrier-based drug delivery systems for cancer therapy and toxicity studies: A review, J Adv Res, vol.15, pp.1-18, 2019.

X. Liu and J. Sun, Endothelial cells dysfunction induced by silica nanoparticles through oxidative stress via JNK/P53 and NF-kappaB pathways, Biomaterials, issue.32, pp.8198-209, 2010.

J. Sergent, V. Paget, and S. Chevillard, Toxicity and genotoxicity of nano-SiO2 on human epithelial intestinal HT-29 cell line, Ann Occup Hyg, vol.2012, issue.5, pp.622-652

M. Cho, W. Cho, M. Choi, S. J. Kim, B. S. Han et al., The impact of size on tissue distribution and elimination by single intravenous injection of silica nanoparticles, Toxicol Lett, vol.189, issue.3, pp.177-83, 2009.

R. Kumar, I. Roy, T. Y. Ohulchanskky, L. A. Vathy, E. J. Bergey et al., In vivo biodistribution and clearance studies using multimodal organically modified silica nanoparticles, ACS Nano, vol.2010, issue.2, pp.699-708

W. Chan, C. Liu, C. Chiau, J. Tsai, S. Liang et al., In vivo toxicologic study of larger silica nanoparticles in mice, Int J Nanomedicine, vol.12, pp.3421-3453, 2017.

T. Liu, L. Li, X. Teng, X. Huang, H. Liu et al., Single and repeated dose toxicity of mesoporous hollow silica nanoparticles in intravenously exposed mice, Biomaterials, vol.32, issue.6, pp.1657-68, 2011.

C. N. Zhou, Mechanisms of tumor necrosis induced by photodynamic therapy, J Photochem Photobiol B, vol.1989, issue.3, pp.299-318

V. P. Skulachev, Mitochondrial physiology and pathology; concepts of programmed death of organelles, cells and organisms, Mol Aspects Med, vol.20, issue.3, pp.139-84, 1999.

X. Li, F. Zhu, J. Jiang, C. Sun, X. Wang et al., Synergistic antitumor activity of withaferin A combined with oxaliplatin triggers reactive oxygen species-mediated inactivation of the PI3K/AKT pathway in human pancreatic cancer cells, Cancer Lett, vol.357, issue.1, pp.219-249, 2015.

I. Baldea, D. E. Olteanu, P. Bolfa, R. M. Ion, N. Decea et al., Efficiency of photodynamic therapy on WM35 melanoma with synthetic porphyrins: Role of chemical structure, intracellular targeting and antioxidant defense, J Photochem Photobiol B, vol.151, pp.142-52, 2015.

A. Roby, S. Erdogan, and V. P. Torchilin, Enhanced in vivo antitumor efficacy of poorly soluble PDT agent, meso-tetraphenylporphine, in PEG-PE-based tumor-targeted immunomicelles, Cancer Biol Ther, vol.6, issue.7, pp.1136-1178, 2007.

P. Liao, Y. Gao, X. Wang, L. Bao, J. Bian et al., Tetraphenylporphyrin derivatives possessing piperidine group as potential agents for photodynamic therapy, J Photochem Photobiol B, vol.165, pp.213-222, 2016.

M. Wu, L. Wu, J. Li, D. Zhang, S. Lan et al., Self-Luminescing Theranostic Nanoreactors with Intraparticle Relayed Energy Transfer for Tumor Microenvironment Activated Imaging and Photodynamic Therapy, Theranostics, vol.2019, issue.1, pp.20-33

F. Janku, D. J. Mcconkey, D. S. Hong, and R. Kurzrock, Autophagy as a target for anticancer therapy, Nat Rev Clin Oncol, vol.8, issue.9, pp.528-567, 2011.

L. Xiong, Z. Liu, G. Ouyang, L. Lin, H. Huang et al., Autophagy inhibition enhances photocytotoxicity of Photosan-II in human colorectal cancer cells, Oncotarget, vol.2017, issue.4, pp.6419-6451

J. Zhu, S. Tian, K. Li, Q. Chen, Y. Jiang et al., Inhibition of breast cancer cell growth by methyl pyropheophenylchlorin photodynamic therapy is mediated though endoplasmic reticulum stress-induced autophagy in vitro and vivo, Cancer Med, vol.7, issue.5, pp.1908-1928, 2018.

X. Ma, Q. Qu, and Y. Zhao, Targeted delivery of 5-aminolevulinic acid by multifunctional hollow mesoporous silica nanoparticles for photodynamic skin cancer therapy, ACS Appl Mater Interfaces, vol.7, issue.20, pp.10671-10677, 2015.

Ö. Er, S. G. Colak, K. Ocakoglu, M. Ince, R. Bresolí-obach et al., Selective Photokilling of Human Pancreatic Cancer Cells Using Cetuximab-Targeted Mesoporous Silica Nanoparticles for Delivery of Zinc Phthalocyanine, Mol Basel Switz, issue.11, p.23, 2018.

S. Biswas and V. P. Torchilin, Nanopreparations for Organelle-Specific Delivery in Cancer, Adv Drug Deliv Rev, vol.66, pp.26-41, 2014.

G. Battogtokh and Y. T. Ko, Mitochondrial-targeted photosensitizer-loaded folate-albumin nanoparticle for photodynamic therapy of cancer, Nanomedicine Nanotechnol Biol Med, vol.13, issue.2, pp.733-776, 2017.

L. Kramer, G. Winter, B. Baur, A. J. Kuntz, T. Kull et al., Quantitative and correlative biodistribution analysis of 89Zr-labeled mesoporous silica nanoparticles intravenously injected into tumor-bearing mice, Nanoscale, vol.2017, issue.27, pp.9743-53

R. Baskaran, J. Lee, and S. Yang, Clinical development of photodynamic agents and therapeutic applications, Biomater Res, vol.22, p.25, 2018.

P. Avci, A. Gupta, M. Sadasivam, D. Vecchio, P. Z. Pam et al., Low-level laser (light) therapy (LLLT) in skin: stimulating, healing, restoring, Semin Cutan Med Surg, vol.32, issue.1, pp.41-52, 2013.

T. Hatakeyama, Y. Murayama, S. Komatsu, A. Shiozaki, Y. Kuriu et al., Efficacy of 5-aminolevulinic acid-mediated photodynamic therapy using light-emitting diodes in human colon cancer cells, Oncol Rep, vol.29, issue.3, pp.911-917, 2013.

W. Zhang, J. Shen, H. Su, G. Mu, J. Sun et al., Co-Delivery of Cisplatin Prodrug and Chlorin e6 by Mesoporous Silica Nanoparticles for Chemo-Photodynamic Combination Therapy to Combat Drug Resistance, ACS Appl Mater Interfaces, vol.8, issue.21, pp.13332-13372, 2016.

W. Zeng, P. Liu, W. Pan, S. R. Singh, and Y. Wei, Hypoxia and hypoxia inducible factors in tumor metabolism, Cancer Lett, vol.356, issue.2, pp.263-270, 2015.

J. Dang, H. He, D. Chen, and L. Yin, Manipulating tumor hypoxia toward enhanced photodynamic therapy (PDT), Biomater Sci, vol.2017, issue.8, pp.1500-1511

R. Jahanban-esfahlan, M. De-la-guardia, D. Ahmadi, and B. Yousefi, Modulating tumor hypoxia by nanomedicine for effective cancer therapy, J Cell Physiol, vol.233, issue.3, pp.2019-2050, 2018.

K. Graham and E. Unger, Overcoming tumor hypoxia as a barrier to radiotherapy, chemotherapy and immunotherapy in cancer treatment, Int J Nanomedicine, vol.13, pp.6049-58, 2018.

N. Lu, W. Fan, X. Yi, S. Wang, Z. Wang et al., Biodegradable Hollow Mesoporous Organosilica Nanotheranostics for Mild Hyperthermia-Induced Bubble-Enhanced Oxygen-Sensitized Radiotherapy, ACS Nano, vol.12, issue.2, pp.1580-91, 2018.

E. Gothié and J. Pouysségur, HIF-1 : régulateur central de l'hypoxie. médecine/sciences, vol.18, pp.70-78, 2002.

J. Kopecka, S. Porto, S. Lusa, E. Gazzano, G. Salzano et al., Self-assembling nanoparticles encapsulating zoledronic acid revert multidrug resistance in cancer cells, Oncotarget, vol.6, issue.31, pp.31461-78, 2015.

R. L. Johnson and J. C. Fleet, Animal models of colorectal cancer, Cancer Metastasis Rev, vol.32, issue.1-2, pp.39-61, 2013.

R. E. Mcintyre, S. Buczacki, M. J. Arends, and D. J. Adams, Mouse models of colorectal cancer as preclinical models, BioEssays News Rev Mol Cell Dev Biol, vol.37, issue.8, pp.909-929, 2015.

N. E. Sharpless and R. A. Depinho, The mighty mouse: genetically engineered mouse models in cancer drug development, Nat Rev Drug Discov, vol.5, issue.9, pp.741-54, 2006.

. .. Remerciements,

. .. Droits-d'auteurs,

. .. Sommaire,

I. Chapitre and . .. Le, 1.1. Localisation, organisation et fonctions du gros intestin

, 2.2.1. Les personnes à risque moyen de cancer colorectal

, Les personnes à risque élevé de cancer colorectal

, Les personnes à risque très élevé de cancer colorectal

I. I. Chapitre and . .. La-thérapie-photodynamique,

B. Ludovic, , 2019.

, Les nanoparticules et la thérapie photodynamique dans le traitement du cancer colorectal

I. .. Chapitre, 2.1. Les caspases, acteurs clés de l'apoptose, 91 IV.1. Les rôles physiologiques de l'apoptose

, La voie des récepteurs de mort ou voie extrinsèque

, 3.1. La mitochondrie, acteur clé de la voie intrinsèque

.. 3. Iv,

V. .. Chapitre,

, L'autophagie médiée par les protéines chaperonnes

V. , Les étapes de la macro-autophagie

, 2.2.1. Le complexe d'élongation Atg12-Atg5-Atg16L1

, La maturation et la fusion de l'autophagosome avec le lysosome

, Le rôle paradoxal de l'autophagie dans les cancers

, L'autophagie, un acteur pro-tumoral

V. 4. and .. .. ,

. .. Projet-de-recherche,

. .. Matériels,

I. Chapitre and . .. Expérimentations-in-vitro, Synthèse de la TPPOH libre et des TPPOH-X SNPs

, Dosage du taux cellulaire d'espèces réactives de l'oxygène

B. Ludovic, , 2019.

I. , Étude de l'internalisation et de la localisation cellulaire

I. , Analyses en microscopie électronique à transmission

I. , Analyse de l'expression

I. , 10.2. Analyse multiparamétrique de l'apoptose grâce à l'annexine V et l'iodure de propidium, Analyse quantitative des caspases 3/7 activées

I. I. Chapitre and .. .. Expérimentations-in-vivo, 1. Création d'un modèle de xénogreffe sous-cutanée de cancer colorectal humain, p.126

, Étude de l'efficacité anti-tumorale et de la biocompatibilité

. .. Partie-expérimentale,

I. Chapitre and . .. Expérimentations-in-vitro, 130 I.2. Dosage du taux cellulaire d'espèces réactives de l'oxygène

, Étude de l'internalisation et de la localisation cellulaire des TPPOH-X SNPs par MET

I. , Étude du potentiel membranaire mitochondrial

I. , Analyse quantitative des caspases 3/7 activées

I. .. Adn, Analyse quantitative de la fragmentation de l

I. , Quantification de l'expression d'acteurs de l'autophagie

I. , Analyse de l'autophagie par MET

I. , Étude du niveau d'apoptose après inhibition de l'autophagie

I. , Analyse quantitative des caspases 3/7 activées après inhibition de l'autophagie, p.176

I. , Analyse quantitative de la fragmentation de l'ADN après inhibition de l'autophagie

I. I. Chapitre and . .. Expérimentations-in-vivo,

I. , Étude de la morphologie et de la structure des tumeurs

I. , Étude de la morphologie et de la structure des tumeurs en fin d'étude

I. , Étude de la prolifération des cellules tumorales en fin d'étude

. .. Discussion, 194 I.1. Intérêt de la vectorisation de la TPPOH par des SNPs

A. Publications-?-ludovic-bretin, S. Pinon, C. Bouramtane, L. Ouk, M. Richard et al., Photodynamic Therapy Activity of New Porphyrin-Xylan-Coated Silica Nanoparticles in Human Colorectal Cancer, Cancers, vol.2019

L. ?-soukaina-bouramtane, A. Bretin, D. Y. Pinon, B. Leger, L. Liagre et al., Porphyrin-xylan-coated silica nanoparticles for anticancer photodynamic therapy, Carbohydrate Polymers, 2019.

, ai réalisé de façon concomitante à mes travaux princeps de recherche les études de viabilité cellulaire ainsi que les analyses de la morphologie cellulaire par MET des 2 composés sur les lignées cellulaires de CCR humain, pp.116-145

?. Ntoutoume, R. Granet, J. Mbakidi, L. Bretin, D. Y. Leger et al., Zinc protoporphyrin IX derivatives bearing one or two adamantane groups: facile synthesis, encapsulation into cyclodextrin/cellulose nanocrystals complexes and phototoxic activity against HT-29 colorectal cancer cell line, ChemMedChem, vol.2019

, Dans cette étude, j'ai réalisé les études d'internalisation cellulaire des 4 composés sur la lignée cellulaire de CCR humain HT-29

P. Laboratoire and . Ea, , vol.7500

P. Laboratoire and . Ea, Faculté des Sciences & Techniques, vol.7500

. Service-d'anatomie-pathologique, , vol.2

L. Bio, E. M. Xlim-umr, and . Cnrs, Rue du Docteur Raymond Marcland, 87025 Limoges Cedex, France; marie-laure.perrin@unilim.fr * Correspondence: bertrand.liagre@unilim.fr Received, vol.7252, 2019.

, Then, cells were exposed or not to PDT with red irradiation and phototoxic e?ects were determined 48 h post-PDT, using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Free TPPOH and TPPOH-X SNPs had no toxic e?ects on HT-29 cells when cells were kept in the dark (Figure 1A). When photoactivated, free TPPOH or TPPOH-X SNPs induced a strong decrease in cell viability in a dose-dependent manner (Figure 1A). However, TPPOH-X SNPs-PDT was more e?ective than free TPPOH-PDT. SNPs alone had no toxic e?ect with or without photoactivation regardless of the concentrations tested (Figure 1B). The same results were seen in HCT116 (Figure S1A,B) and SW620 (Figure S2A,B) cell lines. IC 50 values were calculated in order to compare free TPPOH-PDT vs. TPPOH-X SNPs-PDT. We observed that TPPOH-X SNPs-PDT was much more e?ective than free TPPOH-PDT in HT-29 cells for TPPOH-X SNPs-PDT and around 3 µM for free TPPOH-PDT. HT-29 cells appeared to be the most resistant as IC 50 values for free TPPOH-PDT and TPPOH-X SNPs-PDT were higher than those found for HCT116 and SW620 cell lines (2-and 7-fold respectively). For the following experiments, compounds were used at IC 50 values except for during uptake and localization experiments, SNPs Vectorization Enhanced TPPOH-PDT Phototoxic E?ects Mediated by ROS Production To examine the phototoxicity of TPPOH-PDT in vitro, we treated three human CRC cell lines: HT-29, HCT116, and SW620 with free TPPOH or TPPOH-X SNPs

. Post-pdt, Flow cytometry analyses indicated that exposure of cells to free TPPOH enhanced intracellular ROS levels only after photoactivation (Figure 1C). The median fluorescence intensity of 2',7'-dichlorofluorescein (DCF) after photoactivated free TPPOH treatment was increased compared to free TPPOH and control and was decreased after pretreatment with the ROS scavenger

, SNPs also enhanced intracellular ROS levels only after photoactivation. Pretreatment with NAC decreased further the median fluorescence intensity of DCF (Figure 1D). Free TPPOH-PDT was more e?ective on ROS generation than TPPOH-X SNPs (Figure 1E). In fact, it is well-known complexation of PS to NPs often leads to a decrease of ROS generation through PS quenching, After SNPs vectorization

, Cancers, vol.11, p.27, 1474.

, Then we used a pharmacological inhibitor of autophagy as co-treatment: 3-MA, which can block the early steps of autophagy. Cells treated with TPPOH-X SNPs + 3-MA-PDT expressed lower levels of autophagy-related proteins compared to cells exposed to TPPOH-X SNPs-PDT without co-treatment with 3-MA. Similar results were obtained in HCT116 (Figure S10A) and SW620 cells (Figure S11A). Next, to confirm the induction of autophagy, cells were examined by TEM. Light control cells had an integrated cell nucleus and discrete organelles. However, HT-29 (Figure 4B), HCT116 (Figure S10B), and SW620 cells (Figure S11B) exposed to TPPOH-X SNPs-PDT were seriously damaged with clear cytoplasm vacuolization, with many membrane-bound vesicles containing organelles, cellular fragments, and double-membrane autophagosomes. To determine whether this autophagy induction is a key mediator in resistance to TPPOH-X SNPs-PDT in human CRC cells, we examined whether inhibition of autophagy by 3-MA enhanced TPPOH-X SNPs-PDT-induced apoptosis. First, e?ects of co-treatment with 3-MA on the rate of apoptosis were evaluated by dual staining with Annexin V-FITC and PI by flow cytometry, Autophagy Inhibition Enhanced TPPOH-X SNPs-PDT-Induced Apoptosis For all Western blot figures, please include densitometry readings/intensity ratio of each band; section. Because autophagy is often involved during PDT-treatments, we studied TPPOH-X SNPs-PDT e?ects on autophagy. Western blotting was performed on autophagy-related proteins, Beclin-1, and Atg5, two key regulators of autophagy and light chain 3 (LC3) forms which are involved in autophagosome formation

, Cancers, vol.11, 2019.

, SNPs Vectorization and Autophagy Inhibition Enhanced TPPOH-PDT E?ects on Suppressing CRC Tumor Growth In Vivo To test TPPOH-PDT phototoxic e?ects on tumor growth, we used a xenograft CRC tumor model

, In the control group, tumors exhibited rapid growth after seeding and no significant di?erence in tumor volume between light and non-light tumors was detected. This result indicated that light protocol did not suppressed tumorigenicity in vivo. However, TPPOH-PDT reduced tumor growth compared to TPPOH non-photoactivated treatments in all groups at the end point but with significant di?erences. TPPOH-PDT groups exhibited a slowing of tumor growth after approximately 2-4 days post-PDT. At the end point, free TPPOH-PDT induced a significant reduction in tumor growth by 22.5% ± 1.8% compared to free TPPOH non-PDT. TPPOH-X SNPs-PDT also induced a significant reduction of tumor growth by 37.7% ± 1.4% compared to non-photoactivated TPPOH-X SNPs. However, TPPOH-X SNPs-PDT was significantly more e?ective than free TPPOH-PDT. Moreover, tumor growth inhibition was significantly enhanced by 3-MA co-treatment. TPPOH-X SNPs + 3-MA-PDT significantly decreased tumor growth by 49% ± 1.7% vs. TPPOH-X SNPs + 3-MA non-PDT. However, TPPOH-X SNPs + 3-MA-PDT was significantly more e cient than TPPOH-X SNPs-PDT, with a significant reduction in tumor growth by 19.9% ± 0.3% compared to TPPOH-X SNPs-PDT. In addition, multi TPPOH-X SNPs-PDT were also e cient, p.1

, Mouse body weight showed no significant di?erence between groups over the course of treatment (Figure S12A) indicating no systemic toxicity of free TPPOH or TPPOH-X SNPs. Mice were then sacrificed, and tumors were collected, recorded, and weighed. Tumor weights were consistent with tumor volumes, ± 1.3% compared to mono TPPOH-X SNPs treatment

, Cancers, vol.11, 2019.

, Autophagy is also enhanced in vivo as shown by the increased LC3 immunohistochemistry staining. Pharmacological autophagy inhibition by 3-MA markedly increased PDT-induced cell death in CRC cell lines. Moreover, in vivo autophagy inhibition induced a significant decrease in tumor volume compared to TPPOH-X SNPs-PDT without 3-MA co-treatment. Taken together, these findings suggest that PDT, study, autophagy was involved after TPPOH-X SNPs-PDT in vitro as shown by the overexpression of autophagy-related proteins

, Beclin-1, Atg5 and LC3 antibodies were acquired from Cell Signaling Technology-Ozyme (Saint-Quentin-en-Yvelines). 2',7'-dichlorofluorescein diacetate (DCFDA) cellular ROS detection assay kit and goat anti-rabbit IgG H&L horseradish peroxidase (HRP) secondary antibody were purchased from Abcam, LysoTracker, MitoTracker, rabbit anti-mouse IgG-IgM H&L HRP secondary antibody, TO-PRO-3, annexin V-FITC and propidium iodide (PI) were obtained from Invitrogen-Thermo Fisher Scientific, vol.5, 1960.

, Synthesis of Free TPPOH and TPPOH-X SNPs The synthesis and characterization of free TPPOH and TPPOH-X SNPs were recently published by

, Cells were grown in DMEM medium for HT-29 cells and RPMI 1640 medium for HCT116 and SW620 cells. Cells were supplemented with 10%, Human CRC cell lines (HT-29, HCT116 and SW620) were purchased from the American Type Culture Collection (ATCC-LGC Standards

1. Fbs,

, Cancers, vol.11, 2019.

, After 24 h incubation, cells were treated or not with 3-MA and were irradiated. Cells were recovered 48 h post-PDT and divided in three groups. The first group was used to estimate mitochondrial membrane potential using JC-1

V. Annexin and P. I. , Cells were treated with Annexin V-FITC and PI

, After 24 h incubation, cells were treated or not with 3-MA and were irradiated. Then, cells were treated with caspase-CRC Model To establish a subcutaneous xenograft model of human CRC

T. Tppoh, T. Snps, T. Snps-+-3-ma, and . Multi, HT-29 tumor-bearing mice were established as described above and anticancer treatments were administered when the tumors were approximately 100-150 mm 3 . Mice were randomly divided into five groups (n = 6): control, free, Vivo Antitumor E cacy and Biosafety Evaluation of TPPOH-PDT To confirm antitumor e cacy, p.16

. Then, 24 h post-injection, only one tumor per mouse was subjected to light irradiation to compare intra-individual irradiation e?ects. Consequently, 10 conditions were studied: each of the 5 groups was divided in 2 conditions (no irradiation: PDT-and red irradiation: PDT +). Irradiation was performed with a 660 nm red laser

, At 24 h post-PDT, one mouse from each group except for the TPPOH-X SNPs multi group was sacrificed and tumors were harvested and fixed in 4% paraformaldehyde to prepare para n sections. Hematoxylin/eosin/sa?ron (HES) staining was used for histological analyses, while TUNEL assay and LC3 staining were performed to assess apoptosis and autophagy levels in the tumors, respectively. For other mice

. Globocan, Information and Online Prediction. WHO International Agency for Research of Cancer, 2018.

L. Xue, A. Williamson, S. Gaines, C. Andolfi, T. Paul-olson et al., An Update on Colorectal Cancer. Curr. Probl. Surg, vol.5555, pp.76-116, 2018.

T. Matsuda, K. Yamashita, H. Hasegawa, T. Oshikiri, M. Hosono et al., Recent updates in the surgical treatment of colorectal cancer, Ann. Gastroenterol. Surg, vol.22, pp.129-136, 2018.

B. M. Wolpin and R. J. Mayer, Systemic Treatment of Colorectal Cancer, Gastroenterology, vol.134134, pp.1296-1310, 2008.

Y. T. Lee, Y. J. Tan, and C. E. Oon, Molecular targeted therapy: Treating cancer with specificity, Eur. J. Pharmacol, vol.834, pp.188-196, 2018.

K. Van-der-jeught, H. Xu, Y. Li, X. Lu, and G. Ji, Drug resistance and new therapies in colorectal cancer, World J. Gastroenterol, pp.3834-3848, 2018.

A. Kawczyk-krupka, A. M. Bugaj, W. Latos, K. Zaremba, K. Wawrzyniec et al., Photodynamic therapy in colorectal cancer treatment-The state of the art in preclinical research, Photodiagnosis Photodyn. Ther, vol.13, pp.158-174, 2016.

S. Kwiatkowski, B. Knap, D. Przystupski, J. Saczko, E. K?dzierska et al., Photodynamic therapy-mechanisms, photosensitizers and combinations, Biomed. Pharmacother, vol.106, pp.1098-2107, 2018.

C. C. Licence and . By-nc-nd, Cancers, vol.11, 2019.

M. R. Hamblin and P. Mroz, Advances in Photodynamic Therapy: Basic, Translational and Clinical, 2008.

D. E. Dolmans, D. Fukumura, and R. K. Jain, Photodynamic therapy for cancer, Nat. Rev. Cancer, vol.33, pp.380-387, 2003.

M. C. Derosa and R. J. Crutchley, Photosensitized singlet oxygen and its applications, Coord. Chem. Rev, vol.233, pp.351-371, 2002.

P. Mroz, A. Yaroslavsky, G. B. Kharkwal, and M. R. Hamblin, Cell Death Pathways in Photodynamic Therapy of Cancer, Cancers, vol.33, pp.2516-2539, 2011.

K. Plaetzer, T. Kiesslich, T. Verwanger, and B. Krammer, The Modes of Cell Death Induced by PDT: An Overview, Med. Laser Appl, vol.1818, pp.7-19, 2003.

H. Abrahamse and M. R. Hamblin, New photosensitizers for photodynamic therapy, Biochem. J, vol.473473, pp.347-364, 2016.

R. K. Saini, R. Chouhan, L. P. Bagri, and A. K. Bajpai, Strategies of Targeting Tumors and Cancers, J. Cancer Res. Updates, vol.1, pp.129-152, 2012.

Y. Y. Huang, S. K. Sharma, T. Dai, H. Chung, A. Yaroslavsky et al., Can nanotechnology potentiate photodynamic therapy?, Nanotechnol. Rev, vol.11, pp.111-146, 2012.

A. K. Iyer, G. Khaled, J. Fang, and H. Maeda, Exploiting the enhanced permeability and retention e?ect for tumor targeting, Drug. Discov. Today, vol.1111, pp.812-818, 2006.

Y. Zhou, X. Liang, and Z. Dai, Porphyrin-loaded nanoparticles for cancer theranostics, Nanoscale, vol.8, pp.12394-12405, 2016.

T. A. Debele, S. Peng, and H. Tsai, Drug Carrier for Photodynamic Cancer Therapy, Int. J. Mol. Sci, vol.16, pp.22094-22136, 2015.

X. Wu, M. Wu, and J. Xiaojun-zhao, Recent Development of Silica Nanoparticles as Delivery Vectors for Cancer Imaging and Therapy, Nanomedicine, vol.10, pp.297-312, 2014.

P. Couleaud, V. Morosini, C. Frochot, S. Richeter, L. Raehm et al., Silica-based nanoparticles for photodynamic therapy applications, Nanoscale, vol.2, pp.1083-1095, 2010.
URL : https://hal.archives-ouvertes.fr/hal-00518365

Y. Chen, H. Chen, and J. Shi, In Vivo Bio-Safety Evaluations and Diagnostic/Therapeutic Applications of Chemically Designed Mesoporous Silica Nanoparticles, Adv. Mater, vol.25, pp.3144-3176, 2013.

C. Lemarchand, R. Gref, and P. Couvreur, Polysaccharide-decorated nanoparticles, Eur. J. Pharm. Biopharm, vol.58, pp.327-341, 2004.

R. Gref, Surface-engineered nanoparticles as drug carriers, Synthesis, Functionalization and Surface Treatment of Nanoparticles, pp.233-256, 2002.

D. E. Owens and N. A. Peppas, Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles, Int. J. Pharm, vol.307, pp.93-102, 2006.

A. Shrotri, H. Kobayashi, and A. Fukuoka, Chapter Two-Catalytic Conversion of Structural Carbohydrates and Lignin to Chemicals, Adv. Catal, vol.60, pp.59-123, 2017.

J. Ma, D. Li, L. Zhong, F. Du, J. Tan et al., Synthesis and characterization of biofunctional quaternized xylan-Fe2O3 core/shell nanocomposites and modification with polylysine and folic acid, Carbohydr. Polym, vol.199, pp.382-389, 2018.

S. Daus and T. Heinze, Xylan-based nanoparticles: Prodrugs for ibuprofen release, Macromol. Biosci, vol.10, pp.211-220, 2010.

S. Bouramtane, L. Bretin, A. Pinon, D. Leger, B. Liagre et al., Porphyrin-xylan-coated silica nanoparticles for anticancer photodynamic therapy, Carbohydr. Polym, vol.213, pp.168-175, 2019.

K. Lai, M. C. Killingsworth, and C. S. Lee, The significance of autophagy in colorectal cancer pathogenesis and implications for therapy, J. Clin. Pathol, vol.67, pp.854-858, 2014.

X. Duan, B. Chen, Y. Cui, L. Zhou, C. Wu et al., Ready player one? Autophagy shapes resistance to photodynamic therapy in cancers, Apoptosis, vol.23, pp.587-606, 2018.

C. C. Licence and . By-nc-nd, Cancers, vol.11, 2019.

S. Hackbarth, V. Horne?er, A. Wiehe, F. Hillenkamp, and B. Röder, Photophysical properties of pheophorbide-a-substituted diaminobutane poly-propylene-imine dendrimer, Chem. Phys, vol.269, pp.339-346, 2001.

Y. Li, W. D. Jang, N. Nishiyama, A. Kishimura, S. Kawauchi et al., Dendrimer Generation E?ects on Photodynamic E cacy of Dendrimer Porphyrins and Dendrimer-Loaded Supramolecular Nanocarriers, Chem. Mater, vol.19, pp.5557-5562, 2007.

I. Roy, T. Y. Ohulchanskyy, H. E. Pudavar, E. J. Bergey, A. R. Osero? et al., Ceramic-based nanoparticles entrapping water-insoluble photosensitizing anticancer drugs: A novel drug-carrier system for photodynamic therapy, J. Am. Chem. Soc, vol.125, pp.7860-7865, 2003.

E. Secret, M. Maynadier, A. Gallud, M. Gary-bobo, A. Chaix et al., Anionic porphyrin-grafted porous silicon nanoparticles for photodynamic therapy, Chem. Commun. (Camb, vol.49, pp.4202-4204, 2013.
URL : https://hal.archives-ouvertes.fr/hal-00809285

Z. Youssef, V. Jouan-hureaux, L. Colombeau, P. Arnoux, A. Moussaron et al., Titania and silica nanoparticles coupled to Chlorin e6 for anti-cancer photodynamic therapy, Photodiagnosis Photodyn. Ther, vol.22, pp.115-126, 2018.
URL : https://hal.archives-ouvertes.fr/hal-01925410

S. Bharathiraja, M. S. Moorthy, P. Manivasagan, H. Seo, K. D. Lee et al., Chlorin e6 conjugated silica nanoparticles for targeted and e?ective photodynamic therapy, Photodiagnosis Photodyn. Ther, vol.19, pp.212-220, 2017.

I. Brezániová, K. Záruba, J. Králová, H. Adámková, P. Ulbrich et al., Silica-based nanoparticles are e cient delivery systems for temoporfin, Photodiagnosis Photodyn. Ther, vol.21, pp.275-284, 2018.

V. Simon, C. Devaux, A. Darmon, T. Donnet, E. Thiénot et al., Pp IX silica nanoparticles demonstrate di?erential interactions with in vitro tumor cell lines and in vivo mouse models of human cancers, Photochem. Photobiol, vol.86, pp.213-222, 2010.

V. Kumar, B. Kumar, F. Deeba, S. Bano, A. Kulshreshtha et al., Lipophilic 5-fluorouracil prodrug encapsulated xylan-stearic acid conjugates nanoparticles for colon cancer therapy, Int. J. Biol. Macromol, vol.128, pp.204-213, 2019.

S. Kumar, S. U. Kumar, V. Priyadarshi, R. Gopinath, P. Negi et al., pH-responsive prodrug nanoparticles based on xylan-curcumin conjugate for the e cient delivery of curcumin in cancer therapy, Carbohydr. Polym, vol.188, pp.252-259, 2018.

X. Liu and J. Sun, Endothelial cells dysfunction induced by silica nanoparticles through oxidative stress via JNK/P53 and NF-kB pathways, Biomaterials, vol.31, pp.8198-8209, 2010.

J. Sergent, V. Paget, and S. Chevillard, Toxicity and genotoxicity of nano-SiO 2 on human epithelial intestinal HT-29 cell line, Ann. Occup. Hyg, vol.56, pp.622-630, 2012.

M. Cho, W. S. Cho, M. Choi, S. J. Kim, B. S. Han et al., The impact of size on tissue distribution and elimination by single intravenous injection of silica nanoparticles, Toxicol. Lett, vol.189, pp.177-183, 2009.

R. Kumar, I. Roy, T. Y. Ohulchanskky, L. A. Vathy, E. J. Bergey et al., In vivo biodistribution and clearance studies using multimodal organically modified silica nanoparticles, ACS Nano, vol.4, pp.699-708, 2010.

W. T. Chan, C. C. Liu, J. S. Chiau, S. T. Tsai, C. K. Liang et al., In vivo toxicologic study of larger silica nanoparticles in mice, Int. J. Nanomedicine, vol.12, pp.3421-3432, 2017.

T. Liu, L. Li, X. Teng, X. Huang, H. Liu et al., Single and repeated dose toxicity of mesoporous hollow silica nanoparticles in intravenously exposed mice, Biomaterials, vol.32, pp.1657-1668, 2011.

C. N. Zhou, Mechanisms of tumor necrosis induced by photodynamic therapy, J. Photochem. Photobiol. B, vol.3, pp.299-318, 1989.

S. Elmore, Apoptosis: A review of programmed cell death, Toxicol. Pathol, vol.35, pp.495-516, 2007.

X. Li, F. Zhu, J. Jiang, C. Sun, X. Wang et al., Synergistic antitumor activity of withaferin A combined with oxaliplatin triggers reactive oxygen species-mediated inactivation of the PI3K/AKT pathway in human pancreatic cancer cells, Cancer Lett, vol.357, pp.219-230, 2015.

C. C. Licence and . By-nc-nd, Cancers, vol.11, 2019.

V. P. Skulachev, Mitochondrial physiology and pathology; concepts of programmed death of organelles, cells and organisms, Mol. Asp.S Med, vol.20, pp.139-184, 1999.

L. D. Costa, J. A. De-silva, S. M. Fonseca, C. T. Arranja, A. M. Urbano et al., Photophysical Characterization and in Vitro Phototoxicity Evaluation of 5,10,15,20-Tetra (quinolin-2-yl) porphyrin as a Potential Sensitizer for Photodynamic Therapy, Molecules, vol.21, p.439, 2016.

I. Baldea, D. E. Olteanu, P. Bolfa, R. M. Ion, N. Decea et al., E ciency of photodynamic therapy on WM35 melanoma with synthetic porphyrins: Role of chemical structure, intracellular targeting and antioxidant defense, J. Photochem. Photobiol. B, vol.151, pp.142-152, 2015.

P. Y. Liao, Y. H. Gao, X. R. Wang, L. L. Bao, J. Bian et al., Tetraphenylporphyrin derivatives possessing piperidine group as potential agents for photodynamic therapy, J. Photochem. Photobiol. B, vol.165, pp.213-219, 2016.

A. Roby, S. Erdogan, and V. P. Torchilin, Enhanced in vivo antitumor e cacy of poorly soluble PDT agent, meso-tetraphenylporphine, in PEG-PE-based tumor-targeted immunomicelles, Cancer Biol. Ther, vol.6, pp.1136-1142, 2007.

M. Wu, L. Wu, J. Li, D. Zhang, S. Lan et al., Self-Luminescing Theranostic Nanoreactors with Intraparticle Relayed Energy Transfer for Tumor Microenvironment Activated Imaging and Photodynamic Therapy, Theranostics, vol.9, pp.20-33, 2019.

F. Janku, D. J. Mcconkey, D. S. Hong, and R. Kurzrock, Autophagy as a target for anticancer therapy, Nat. Rev. Clin. Oncol, vol.8, pp.528-539, 2011.

Q. Xue, X. Wang, P. Wang, K. Zhang, and Q. Liu, Role of p38MAPK in apoptosis and autophagy responses to photodynamic therapy with Chlorin e6, Photodiagnosis Photodyn. Ther, vol.12, pp.84-91, 2015.

L. Xiong, Z. Liu, G. Ouyang, L. Lin, H. Huang et al., Autophagy inhibition enhances photocytotoxicity of Photosan-II in human colorectal cancer cells, Oncotarget, vol.8, pp.6419-6432, 2017.

M. F. Wei, M. W. Chen, K. C. Chen, P. J. Lou, S. Y. Lin et al., Autophagy promotes resistance to photodynamic therapy-induced apoptosis selectively in colorectal cancer stem-like cells, Autophagy, vol.10, pp.1179-1192, 2014.

P. Tu, Q. Huang, Y. Ou, X. Du, K. Li et al., Aloe-emodin-mediated photodynamic therapy induces autophagy and apoptosis in human osteosarcoma cell line MG-63 through the ROS/JNK signaling pathway, Oncol. Rep, vol.35, pp.3209-3215, 2016.

J. Zhu, S. Tian, K. T. Li, Q. Chen, Y. Jiang et al., Inhibition of breast cancer cell growth by methyl pyropheophenylchlorin photodynamic therapy is mediated though endoplasmic reticulum stress-induced autophagy in vitro and vivo, Cancer Med, vol.7, 1908.

C. Lepage, D. Y. Léger, J. Bertrand, F. Martin, J. L. Beneytout et al., Diosgenin induces death receptor-5 through activation of p38 pathway and promotes TRAIL-induced apoptosis in colon cancer cells, Cancer Lett, vol.301, pp.193-202, 2011.

J. Lu, M. Liong, Z. Li, J. I. Zink, F. Tamanoi et al., Biodistribution, and Drug-Delivery E ciency of Mesoporous Silica Nanoparticles for Cancer Therapy in Animals, Small, vol.6, pp.1794-1805, 2010.

, Guidance Document on Using In Vitro Data to Estimate In Vivo Starting Doses for Acute Toxicity. NIH Publication No. 01-4500, 2001.

C. C. Licence and . By-nc-nd, Cancers, vol.11, 2019.

J. Li, N. Hou, A. Faried, S. Tsutsumi, and H. Kuwano, Inhibition of autophagy augments 5-fluorouracil chemotherapy in human colon cancer in vitro and in vivo model, Eur. J. Cancer, vol.46, pp.1900-1909, 2010.

C. Fidanzi-dugas, B. Liagre, G. Chemin, A. Perraud, C. Carrion et al., Analysis of the in vitro and in vivo e?ects of photodynamic therapy on prostate cancer by using new photosensitizers, protoporphyrin IX-polyamine derivatives, Biochim. Biophys. Acta, vol.1861, pp.1676-1690, 2017.

, This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license, © 2019 by the authors. Licensee MDPI

C. C. Licence and . By-nc-nd, 27 (q, 2H, J = 6.5 Hz, H? eCH2?), 2.66 (t, 2H, eluent: petroleum ether/CHCl3 from 80 to 100%) a pure porphyrin 2 with 91% yield. Rf = 0.44 (CHCl3), 1 H NMR (CDCl3, 500.15 MHz) ?H, vol.2

, OeCH2); 112.72 (C-3,5 aryl), C meso, vol.60, p.3

, C-2,6 aryl); 135.59 (C-1 aryl), vol.134, pp.19-142

. Uv-vis, MS (ESI): m/z = 745, UV-vis (CHCl3) ? max nm (?, 10 3 L mol ?1 cm ?1, vol.553, p.20

, Compound 2 (0.3 g, 1 equiv, 0.4 mmol) was dissolved in 15 mL DMF

). Mhz, ?. , J. =-8-hz-;-t,-2h, C. , and J. , , vol.2

). Mhz and . ?c, MS (ESI), vol.1, p.647

H. Abrahamse and M. R. Hamblin, New photosensitizers for photodynamic therapy, Biochemical Journal, vol.473, pp.347-364, 2016.

S. Bharathiraja, M. S. Moorthy, P. Manivasagan, H. Seo, K. D. Lee et al., , 2017.

, Chlorin e6 conjugated silica nanoparticles for targeted and effective photodynamic therapy, Photodiagnosis and Photodynamic Therapy, vol.19, pp.212-220

R. Bonnett, Photosensitizers of the porphyrin and phthalocyanine series for photodynamic therapy, Chemical Society Reviews, vol.24, pp.19-33, 1995.

R. Boscencu, D. Licsandru, R. Socoteanu, A. S. Oliveira, and L. F. Ferreira, Synthesis and spectral characterization of some unsymmetrically-substituted mesoporphyrinic compounds, Revista de Chimie, vol.58, pp.498-501, 2007.

I. Brezániová, K. Záruba, J. Králová, A. Sinica, H. Adámková et al., , 2018.

, Silica-based nanoparticles are efficient delivery systems for temoporfin, Photodiagnosis and Photodynamic Therapy, vol.21, pp.275-284

V. Chaleix, P. Couleaud, V. Sol, R. Zerrouki, S. Alves et al., Microwaveassisted expeditious O-alkylation of meso-hydroxyphenylporphyrins, Journal of Porphyrins and Phthalocyanines, vol.13, pp.888-892, 2009.
URL : https://hal.archives-ouvertes.fr/hal-00696084

A. G. Coombes, S. Tasker, M. Lindblad, J. Holmgren, K. Hoste et al., Biodegradable polymeric microparticles for drug delivery and vaccine formulation: The surface attachment of hydrophilic species using the concept of poly (ethylene glycol) anchoring segments, Biomaterials, vol.18, pp.1153-1161, 1997.

S. Daus and T. Heinze, Xylan-based nanoparticles: Prodrugs for ibuprofen release, Macromolecular Bioscience, vol.10, pp.211-220, 2010.

T. A. Debele, S. Peng, and H. C. Tsai, Drug carrier for photodynamic cancer therapy, International Journal of Molecular Sciences, vol.16, pp.22094-22136, 2015.

N. Drogat, R. Granet, C. Le-morvan, G. Bégaud-grimaud, P. Krausz et al., , 2012.

, Chlorin-PEI-labeled cellulose nanocrystals: Synthesis, characterization and potential application in PDT, Bioorganic & Medicinal Chemistry Letters, vol.22, pp.3648-3652

A. Ebringerová, Z. Hromádková, and T. Heinz, Hemicellulose. Advances in Polymer Science, vol.186, pp.1-67, 2005.

S. Elmore, Apoptosis: A review of programmed cell death, Toxicologic Pathology, vol.35, pp.495-516, 2007.

M. M. Frank and L. F. Fries, The role of complement in inflammation and phagocytosis, Immunology Today, vol.12, pp.322-326, 1991.

R. Gref, Y. Minamitake, M. T. Peracchia, V. Trubetskoy, V. Torchilin et al., Biodegradable long-circulating polymeric nanospheres, Science, vol.263, pp.1600-1603, 1994.

B. W. Henderson and T. J. Dougherty, How does photodynamic therapy work? Photochemistry and Photobiology, vol.55, pp.145-157, 1992.

D. J. Kerrouche, T. Sadoun, G. Stoclet, V. Sol, V. Gloaguen et al., Synthesis and characterization of xylan-graft-poly(L-lactide), International Journal of Polymer Analysis and Characterization, vol.23, pp.193-206, 2018.

S. Kwiatkowski, B. Knap, D. Przystupski, J. Saczko, E. K?dzierska et al., Photodynamic therapy-Mechanisms, photosensitizers and combinations, 2018.

, Biomedicine & Pharmacotherapy, vol.106, pp.1098-1107

J. Kydd, R. Jadia, P. Velpurisiva, A. Gad, S. Paliwal et al., Targeting strategies for the combination treatment of cancer using drug delivery systems, European Journal of Pharmaceutics and Biopharmaceutics, vol.9, pp.327-341, 2004.

R. G. Little, J. A. Anton, P. A. Loach, and J. A. Ibers, The synthesis of some substituted tetraarylporphyrins, Journal of Heterocyclic Chemistry, vol.12, pp.343-349, 1975.

J. Ma, D. Li, L. Zhong, F. Du, J. Tan et al., Synthesis and characterization of biofunctional quaternized xylan-Fe2O3 core/shell nanocomposites and modification with polylysine and folic acid, Carbohydrate Polymers, vol.199, pp.382-389, 2018.

H. Maeda, The enhanced permeability and retention (EPR) effect in tumor vasculature: The key role of tumor-selective macromolecular drug targeting, Advances in Enzyme Regulation, vol.41, pp.189-207, 2001.

H. Maeda and Y. Matsumura, Tumoritropic and lymphotropic principles of macromolecular drugs, Critical Reviews in Therapeutic Drug Carrier Systems, vol.6, pp.193-210, 1989.

M. Managa, J. Mack, D. Gonzalez-lucasb, S. Remiro-buenamañana, C. Tshangana et al., , 2016.

, TEM analysis of HCT116 cells (a) control cell (irradiated) (b) PX SNPs (dark), (c) PX SNPs

, White arrows indicate SNPs inside cytoplasm

S. Bouramtane,

, Licence CC BY-NC-ND 3.0 tetraphenylporphyrinsubphthalocyanine conjugates, Journal of Porphyrins and Phtalocyanines, vol.20, pp.1-20

Y. Matsumura and H. Maeda, A new concept for macromolecular therapeutics in cancer chemotherapy: Mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs, Cancer Research, vol.46, pp.6387-6392, 1986.

J. Mbakidi, K. Herke, S. Alvès, V. Chaleix, R. Granet et al., Synthesis and photobiocidal properties of cationic porphyrin-grafted paper, Carbohydrate Polymers, vol.99, pp.333-338, 2013.
URL : https://hal.archives-ouvertes.fr/hal-00800880

R. F. Melo-silveira, G. P. Fidelis, M. S. Pereira-costa, C. B. Silva-telles, N. Dantas-santos et al., In vitro antioxidant, anticoagulant and antimicrobial activity and in inhibition of cancer cell proliferation by xylan extracted from corn cobs, International Journal of Molecular Sciences, vol.13, pp.409-426, 2012.

C. Moine, P. Krausz, V. Chaleix, O. Sainte-catherine, M. Kraemer et al., Structural characterization and cytotoxic properties of a 4-O-methylglucuronoxylan from castanea sativa, Journal of Natural Products, vol.70, pp.60-66, 2007.
URL : https://hal.archives-ouvertes.fr/hal-00416637

F. S. Mozar and E. H. Chowdhury, PEGylation of carbonate apatite nanoparticles prevents opsonin binding and enhances tumor accumulation of gemcitabine, Journal of Pharmaceutical Sciences, vol.107, pp.2497-2508, 2018.

H. Nagai and Y. H. Kim, Cancer prevention from the perspective of global cancer burden patterns, Journal of Thoracic Disease, vol.9, pp.448-451, 2017.

M. Österberg, J. Laine, P. Stenius, A. Kumpulainen, and P. M. Claesson, Forces between xylan-coated surfaces: Effect of polymer charge density and background electrolyte, Journal of Colloid and Interface Science, vol.242, pp.59-66, 2001.

D. E. Owens and N. A. Peppas, Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles, International Journal of Pharmaceutics, vol.307, pp.93-102, 2005.

M. T. Peracchia, E. Fattal, D. Desmaële, M. Besnard, J. P. Noël et al., Stealth PEGylated polycyanoacrylate nanoparticles for intravenous administration and splenic targeting, Journal of Controlled Release, vol.60, pp.121-128, 1999.

C. Ringot, N. Saad, F. Brégier, P. Bressollier, E. Poli et al., Antibacterial activity of a photosensitive hybrid cellulose fabric, Photochemical and Photobiological Sciences, vol.17, pp.1780-1786, 2018.

I. Roy, T. Y. Ohulchanskyy, H. E. Pudavar, E. J. Bergey, A. R. Oseroff et al., Ceramic-based nanoparticles entrapping water-insoluble photosensitizing anticancer drugs: A novel drug-carrier system for photodynamic therapy, Journal of the American Chemical Society, vol.125, pp.7860-7865, 2003.

R. K. Saini, R. Chouhan, L. P. Bagri, and A. K. Bajpai, Strategies of targeting tumors and cancers, Journal of Cancer Research Updates, vol.1, pp.129-152, 2012.

E. D. Sternberg, D. Dolphin, and C. Brückner, Porphyrin-based photosensitizers for use in photodynamic therapy, Tetrahedron, vol.54, pp.4151-4202, 1998.

W. Stöber, A. Fink, and E. Bohn, Controlled growth of monodisperse silica spheres in the micron size range, Journal of Colloid and Interface Science, vol.26, pp.62-69, 1968.

B. I. Tamba, A. Dondas, M. Leon, A. N. Neagu, G. Dodi et al., Silica nanoparticles: Preparation, characterization and in vitro/in vivo biodistribution studies, European Journal of Pharmaceutical Sciences, vol.71, pp.46-55, 2015.

F. Yan and R. Kopelman, The embedding of meta-tetra(hydroxyphenyl)-chlorin into silica nanoparticle platforms for photodynamic therapy and their singlet oxygen production and pH-dependent optical properties, Photochemistry and Photobiology, vol.78, pp.587-591, 2003.

T. Yan, J. Cheng, Z. Liu, F. Cheng, X. Wei et al., pH-sensitive mesoporous silica nanoparticles for chemo-photodynamic combination therapy, Colloids and Surfaces B. Biointerfaces, vol.161, pp.442-448, 2017.

A. Zhu, L. Yuan, W. Jin, S. Dai, Q. Wang et al., Polysaccharide surface modified Fe3O4 nanoparticles for camptothecin loading and release, Acta Biomaterialia, vol.5, pp.1489-1498, 2009.

S. Bouramtane,