Optimisation de la thérapie photodynamique par la nanovectorisation du photosensibilisateur mTHPC à l’aide de vésicules extracellulaires

Abstract : Photodynamic therapy (PDT) is an alternative treatment to surgery in oncology using photosensitizer (PS), light and oxygen. Meta-tetra(hydroxylphenyl)chlorin (mTHPC) is one of the most used PS in clinics due to its high absorption in the deep red and high 1O2 quantum yield. In order to improve the mTHPC tumor selectivity different attempts of nanovectorisation were conducted. Non-PEGylated liposomal mTHPC (Foslip®) increase biodistribution and pharmacokinetic properties. However, the rapid liposome destruction during circulation and rapid mTHPC release are obvious shortcomings. Alternatively, mTHPC vectorization could be realized by extracellular vesicles (EVs). Derived from the cell, EVs possess a natural stability in bloodstream and ability to transport and deliver cargo molecules into cancer cells. This formulation is interesting for PDT due to the ability to encapsulate porphyrins. The aim of the present study was to determine the interest of EVs as mTHPC nanocarriers in various preclinical models compared to Foslip®. In contrast to Foslip®, membrane integrity of mTHPC-EVs was conserved in 20% of plasma. In vitro, mTHPC-EVs showed cellular internalization by an active endocytosis mechanism. In a 3D model of spheroids, mTHPC-EVs have improved cellular uptake, better diffusion inside spheroid and increased PDT efficacy. In vivo, mTHPC-EVs appeared to be more potent in terms of PDT efficacy, with a tumor growth delay significantly higher. In conclusion, integration of mTHPC in EVs improves PDT efficacy in various preclinical models. The tracking of mTHPC-EVs using a radioactive tracer in xenografted rodents as well as the study of vascularization targeting will be studied in the next step of this work.
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https://hal.univ-lorraine.fr/tel-02131239
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Submitted on : Thursday, May 16, 2019 - 11:59:18 AM
Last modification on : Saturday, May 18, 2019 - 1:25:59 AM

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  • HAL Id : tel-02131239, version 1

Citation

Marie Millard. Optimisation de la thérapie photodynamique par la nanovectorisation du photosensibilisateur mTHPC à l’aide de vésicules extracellulaires. Cancer. Université de Lorraine, 2018. Français. ⟨NNT : 2018LORR0246⟩. ⟨tel-02131239⟩

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