Paclitaxel controlled delivery using a pH-responsive functional-AuNP/block-copolymer vesicular nanocarrier composite system

摘要

Paclitaxel (PTX)-loaded gold nanoparticles functionalized with mercaptooctanoic acid (MOA) and folic acid (FA) (AuMOA-FA) were encapsulated within pH-sensitive poly(2-vinylpyridine)-b-poly(ethylene oxide) (P2VP-PEO) vesicles with the aim to develop a more selective injectable nano-formulation for PTX, lacking the side effects of the conventional PTX delivery system. The size of the resulting composite vesicles was lower than 200 nm, i.e. it is suitable for tumor targeting applications taking advantage of the enhanced permeability and retention (EPR) effect. The vesicles did not aggregate in the presence of high electrolyte concentrations, indicating the colloidal stability of the vesicles. The vesicles did not leak their AuMOA-FA or PTX content at physiological pH of 7.4. However, AuMOA-FA and PTX release were significantly accelerated at acidic pHs resembling tumor environment and acidic intracellular compartments. PTX release from the vesicles at acidic pH apparently follows AuMOA-FA release from the vesicles. Flow cytometry measurements and confocal laser scanning microscopy images showed that the vesicles could enter A549 cancer cells in culture and that cellular uptake increased with time. Blank vesicles did not exhibit cytotoxicity and did not induce apoptosis in A549 cancer cells. The PTX currying vesicles exhibited comparable or a little higher cytotoxicity than free PTX. Both the PTX currying vesicles and free PTX induced A549 cells apoptosis, however the vesicle-encapsulated PTX induced a higher percentage of late apoptotic cells than free PTX.