Peroxisome-inspired T4 phage hybrid enzyme nanoreactors for photodynamic therapy of breast cancer

The peroxisome is an important organelle for H 2 O 2 metabolism and O 2 redistribution in organisms. Drawing inspiration from this biochemical pathway, a T4-Ce6-Cat-Lox (TCCL) simpler biomimetic peroxisome was constructed using the T4 phage’s Soc and Hoc sites to enhance photodynamic therapy (PDT). The cascading catalytic system of lactate oxidase (Lox) and catalase (Cat) was displayed on the phage architecture through in vitro phage display technology. 720 Lox molecules and 95 Cat molecules displayed on the T4 phage can be precisely controlled by the feed concentration. The enzymatic reaction of Lox, triggered by lactic acid in the tumor microenvironment, generated H 2 O 2 at the Soc site. Subsequently, the H 2 O 2 was decomposed into O 2 by Cat at the Hoc site. By manipulating the cascading catalytic system ratio of Lox and Cat to 7.5:1, the ROS generation efficiency of Ce6 was as high as 99.2 %, and the tumor inhibition rate reached 91.25 %. More importantly, the TCCL was constructed by natural T4 nanocarrier, exhibiting good biocompatibility and low immunogenicity in vivo . This study explored the construction of a simplified biomimetic peroxisome using the T4 phage display technology and provided a promising strategy for cascading catalytic system construction.