mTHPC-loaded extracellular vesicles outperform liposomal and free mTHPC formulations by an increased stability, drug delivery efficiency and cytotoxic effect in tridimensional model of tumors

AbstractEfficient photodynamic therapy with meta-tetra(hydroxyphenyl)chlorine requires the application of specific nanoformulations. mTHPC liposomal formulation (Foslip®) demonstrated favorable pharmacokinetics properties. However, rapid liposomes destruction in circulation and rapid mTHPC release impedes Foslip® applications. Alternatively, mTHPC nanovectorization using extracellular vesicles (EVs) could be an attractive option. EVs are naturally secreted by the organism to play a role in intercellular communication due to the capacity to transport proteins and nucleic acids. EVs also possess a natural ability to deliver therapeutic molecules into cancer cells. The aim of the present study was to evaluate photophysical and photobiological properties of mTHPC loaded in endothelial EVs as nanocarriers. We also studied efficiency of nanovectorisation on mTHPC distribution and PDT activity in multicellular tumor spheroids (MCTSs). MCTS is a nonvascularized in vitro 3D model of cells that mimics a similar mic...