HAL will be down for maintenance from Friday, June 10 at 4pm through Monday, June 13 at 9am. More information
Skip to Main content Skip to Navigation
Journal articles

mTHPC-loaded extracellular vesicles significantly improve mTHPC diffusion and photodynamic activity in preclinical models

Abstract : Extracellular vesicles (EVs), derived from the cell, display a phospholipid bilayer membrane that protects the cargo molecules from degradation and contributes to increasing their stability in the bloodstream and tumor targeting. EVs are interesting in regard to the delivery of photosensitizers (PSs) used in the photodynamic therapy (PDT), as they allow us to overcome the limitations observed with liposomes. In fact, liposomal formulation of meta-tetra(hydroxyphenyl)chlorin (mTHPC) (Foslip®), one of the most potent clinically approved PSs, is rapidly destroyed in circulation, thus decreasing in vivo PDT efficacy. mTHPC-EV uptake was evaluated in vitro in a 3D human colon HT-29 microtumor and in vivo study was performed in HT-29 xenografted mice. The obtained data were compared with Foslip®. After intravenous injection of the mTHPC formulations, biodistribution, pharmacokinetics and PDT-induced tumor regrowth were evaluated. In a 3D model of cells, mTHPC-EV uptake featured a deeper penetration after 24h incubation compared to liposomal mTHPC. In vivo results showed a considerable improvement of 33% tumor cure with PDT treatment applied 24h after injection, while 0% was observed after Foslip®/PDT. Moreover, 47 days were required to obtain ten times the initial tumor volume after mTHPC-EVs/PDT compared to 30 days for liposomal mTHPC. In conclusion, compared to Foslip®, mTHPC-EVs improved mTHPC biodistribution and PDT efficacy in vivo. We deduced that a major determinant factor for the improved in vivo PDT efficacy is the deep mTHPC intratumor penetration.
Document type :
Journal articles
Complete list of metadata

https://hal.archives-ouvertes.fr/hal-02916946
Contributor : Henri-Pierre Lassalle Connect in order to contact the contributor
Submitted on : Tuesday, August 18, 2020 - 11:23:19 AM
Last modification on : Thursday, April 7, 2022 - 1:58:18 PM

Links full text

Identifiers

Citation

Marie Millard, Solène Posty, Max Piffoux, Jordane Jasniewski, Henri-Pierre Lassalle, et al.. mTHPC-loaded extracellular vesicles significantly improve mTHPC diffusion and photodynamic activity in preclinical models. Pharmaceutics, MDPI, 2020, 12 (7), pp.676. ⟨10.3390/pharmaceutics12070676⟩. ⟨hal-02916946⟩

Share

Metrics

Record views

57