A tumoral acidic pH-responsive drug delivery system based on a novel photosensitizer (fullerene) for in vitro and in vivo chemo-photodynamic therapy

Abstract

Fullerene has shown great potential both in drug delivery and photodynamic therapy. Herein, we developed a doxorubicin (DOX)-loaded poly(ethyleneimine) (PEI) derivatized fullerene (C60–PEI–DOX) to facilitate combined chemotherapy and photodynamic therapy in one system, and DOX was covalently conjugated onto C60–PEI by the pH-sensitive hydrazone linkage. The release profiles of DOX from C60–PEI–DOX showed a strong dependence on the environmental pH value. The biodistributions of C60–PEI–DOX were investigated by injecting CdSe/ZnS (Qds) labeled conjugates (C60–PEI–DOX/Qds) into tumor-bearing mice. C60–PEI–DOX/Qds showed a higher tumor targeting efficiency compared with Qds alone. Compared with free DOX in an in vivo murine tumor model, C60–PEI–DOX afforded higher antitumor efficacy without obvious toxic effects to normal organs owing to its good tumor targeting efficacy and the 2.4-fold greater amount of DOX released in the tumor than in the normal tissues. C60–PEI–DOX also showed high antitumor efficacy during photodynamic therapy. The ability of C60–PEI–DOX nanoparticles to combine local specific chemotherapy with external photodynamic therapy significantly improved the therapeutic efficacy of the cancer treatment, the combined treatment demonstrating a synergistic effect. These results suggest that C60–PEI–DOX may be promising for high treatment efficacy with minimal side effects in future therapy.