Combretastatin A4-combined photodynamic therapy for enhanced tumor therapeutic efficacy

Abstract

The limitation of traditional photodynamic therapy (PDT) such as the inherent hypoxia, the light penetration and the photosensitizer’s activity make it difficult to achieve a satisfactory therapeutic effect. To overcome these restrictions and enhance the antitumor therapeutic effect, the combination of PDT with other means offers a promising strategy to improve the efficacy of PDT. Herein, biodegradable poly (L-glutamic acid) (PLG) was used to chemically conjugate hydrophobic photosensitizers (TPP-NH2) and vascular disrupting agents (CA4) to prepare polymer-drug conjugates PT and PC, respectively. Both the solubility of drug and the endocytosis ability of nanoparticles have been enhanced. When the tumor was treated by PC and PT simultaneously, the conjugated TPP-NH2 and CA4 would be released from the internalized PC and PT due to the degradation of PLG. Under laser irradiation, the released TPP-NH2 could mainly kill the marginal tumor cells by generating cytotoxic singlet oxygen, while the released CA4 caused necrosis in the central region of the tumor by blocking the blood vessels. In vivo and in vitro analysis showed that this combined administration strategy exhibited more satisfied anti-proliferative effect compared to monotherapy, providing an effective strategy to develop synergistic cancer therapy.