Efficient delivery of photosensitizers and hypoxic prodrugs for tumor combination therapy by membrane camouflage nanoparticles

Abstract: Photodynamic therapy (PDT) is an oxygen-dependent, non-invasive cancer treatment. The hypoxia in the tumor environment limited the therapeutic effects of PDT. Combined delivery of hypoxic prodrugs and photosensitizers is a promising approach to enhance the PDT efficiency. In this paper, an erythrocyte and tumor cell membrane camouflage nanocarrier co-loaded with photosensitizer (Indocyanine green) and hypoxic prodrug (Tirapazamine), which was used to combine PDT with chemotherapy. The system achieves less macrophage clearance through erythrocyte membranes and tumor-targeted tumor cell membranes, thereby inducing the cell death and increasing tumor environment hypoxia by NIR irradiation of photosensitizers. Furthermore, TPZ under hypoxia kills cells by producing stable free radical intermediate cytotoxic substances, and free radicals be prone to oxidize rapidly back to the parent molecule. In vivo results showed that the tumor inhibition rate of the drug-loaded nanoparticles increased from 34% to 64% after membrane modification. Moreover, the tumor inhibition rate of the photodynamic treatment group alone was only 47%, and the tumor inhibition rate after the combination was 1.3 times that of photodynamic therapy alone. Our platform is expected to contribute to the further application of cancer combination therapy.