MTHPC-based biodegradable nanoparticles for cancer treatment

Abstract

A serious limitation of photodynamic therapy (PDT) is the absence of specific cancer targeting, resulting in an excessive tissue destruction, which can provoke life threatening situations. To partially overcome these constraints, incorporation of the active compound into liposomal nanoparticles can be proposed. Embedding of active drugs in liposomes favours passive targeting of tumors through Enhanced Permeability Retention (EPR) effect. Liposomal formulations of mTHPC (Foslip®) enable a more selective and faster accumulation of drugs in the tumors, with a faster clearance, together with at least similar to liposomes-free mTHPC therapeutic efficacy. Best Foslip® - photoinduced response was obtained from the study of spatial intratumoral Foslip distribution rather than from bulk pharmacological tissues pharmacokinetics. Comprehension of the transport kinetics of the photosensitizer from the vessels towards extravascular structures is essential for optimizing clinical protocols. We have observed different redistribution patterns of mTHPC to plasma components according to liposomal composition (conventional vs. pegylated liposomes) in vitro. The visualization of these processes in real time in vivo using the chick chorio allantoic membrane (CAM) model corroborate with in vivo results. Future directions consist in aptamer-mediated targeted delivery of chlorin types photosensitizers to tumor tissues. --------------------------------------------------------------------------------