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Conception de nouveaux bioconjugués "squalénisés" anticancéreux dotés de propriétés d'auto-assemblage : synthèse, caractérisation des nanoparticules et évaluation biologique

Abstract : Squalenoylation is a strategy of vectorization consisting in coupling squalene derivatives tohydrophylic drugs as nucleoside analogues. The amphiphilic conjugates obtained are able to selfassembleinto nanoparticles with a diameter of 100 nm in water. In addition those nanoparticleshave shown impressive anticancer and antiviral activities. Our objective was to extend this strategyto different anticancer drugs as antimetabolites, antimitotics and alkylating agents. Differentsqualenoyl derivatives have been synthesised and then coupled to drugs to furnish thecorresponding squalenoylated biconjugates. It has been shown that those prodrugs were able toself-assemble into nanoparticles in water. Nanoparticles of the bioconjugates are active in vitro ondifferent human cancer cell lines and in vivo in Mice on different cancer models. Squalenoylation hasfinally been extended to numerous anticancer drugs, proving that this strategy is a general methodof vectorization with a high therapeutic potential.
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https://tel.archives-ouvertes.fr/tel-00819390
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Submitted on : Wednesday, May 1, 2013 - 1:01:30 AM
Last modification on : Friday, October 23, 2020 - 4:55:08 PM
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  • HAL Id : tel-00819390, version 1

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Joachim Caron. Conception de nouveaux bioconjugués "squalénisés" anticancéreux dotés de propriétés d'auto-assemblage : synthèse, caractérisation des nanoparticules et évaluation biologique. Autre. Université Paris Sud - Paris XI, 2011. Français. ⟨NNT : 2011PA114825⟩. ⟨tel-00819390⟩

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