Self-assembling gelatin based delivery of multienzyme activity nanozyme and photosensitizer for ROS storm based cancer therapy.

ABSTRACT

Nanozymes with multienzyme activity for reactive oxygen species (ROS) generation and intracellular redox imbalance are attractive strategy for cancer therapy. However, it is severely limited by low biocompatibility and catalytic efficiency, hypoxic and high levels of GSH in the tumor microenvironment. To address these issues, a copper doping carbon nanozyme (CC) with multienzyme activity was designed and integrated with photosensitizer Ce6 and gelatin to fabricate ROS amplifier (CCC). Gelatin endowed CCC with good biocompatibility, low hemolysis, and enzyme responsive degradation. CCC with high CAT-like, POD-like, OXD-like, and GSHox-like activities can induce the intracellular ROS storm formation to eliminate the cancer cells. The OXD-like activity and PDT performance mediated 1O2 generation was markedly potentiated by the CAT-like activity of CCC via catalyzing high expression of H2O2 to generate O2. At the same time, a large amount of ·OH were produced through POD-like activity of CCC and GSH was depleted by the GSHox-like activities of CCC, resulting in a destructive ROS storm formation and cellular redox homeostasis disruption. Both in vivo and in vitro experiments showed that CCC displayed satisfactory anti-tumor activity and biocompatibility. Our work provides a novel strategy for the development of nanozyne enhanced photodynamic therapy of cancer.