Iridium photosensitizer constructed liposomes with hypoxia-activated prodrug to destrust hepatocellular carcinoma

Hypoxic tumor microenvironment is a major challenge for photodynamic therapy (PDT). To overcome this problem, PDT combined hypoxia-activated chemotherapy is a promising strategy for hypoxic cancer therapy. Herein, a multifunctional liposome (AQ4N-Ir1-sorafenib-liposome) is prepared by encapsulating a hypoxia-activated prodrug AQ4N, a photosensitizer iridium(III) complex and hepatocellular carcinoma (HCC) targeting drug sorafenib, for synergistic therapy of HCC. Ir1-mediated PDT upon irradiation induces ROS generation and hypoxic environment, which leads to the disassembly of the liposome and activates the antitumor activity of AQ4N. Meantime, the co-delivered sorafenib could effectively target therapy of HCC. It is noted that ferroptosis mechanism is proved during the treatment. This work contributes to the design of hypoxia-responsive multifunctional liposome for combination of chemotherapy, targeting therapy and PDT. It is a promising strategy for hypoxic HCC therapy.