Tumor microenvironment triggered local oxygen generation and photosensitizer release from manganese dioxide mineralized albumin-ICG nanocomplex to amplify photodynamic immunotherapy efficacy

Abstract

Abstract Photodynamic therapy (PDT) has emerged as a potential clinical strategy for tumor therapy. It can generate reactive oxygen species (ROS) to cause the chemical damage of tumor cells and promote the immune killing effects of T cells on tumor cells in the presence of enough oxygen and PDT drugs. However, most solid tumors are in a state of oxygen deficiency, which seriously limit the efficacy of PDT in generation enough ROS. Besides, few safe PDT drugs with ideal pharmacokinetic behavior are available in the clinic, which severely limits the clinical transformation and application of PDT. Herein, we utilized manganese chloride to mineralize the hydrophilic indocyanine green/albumin polyplexes (ICG@BSA@MnO2) by using bio-mineralized method to solve these problems of PDT. These ICG@BSA@MnO2 nanoparticles could circulate in the blood for a long period other than quickly removed from body after 30 min like free ICG. When accumulated at the tumor site, ICG was responsively released in the presence of hydrogen peroxide. Apart this, the tumor hypoxia microenvironment was also reversed owing to enhanced O2 generation by the reaction of MnO2 with hydrogen peroxide. Benefits from the rich accumulation of ICG and ameliorated tumor hypoxia in the tumor sites, the enhanced generation of ROS could successfully promote the distribution of CD3+ and CD8+ T cells inside the tumors, which then lead to the amplified efficacy of PDT in both CT26 and B16F10 tumor models without causing any side effects.