T4 Phage Display Technology for Enhanced Photodynamic Therapy of Breast Cancer

Hypoxia in tumor tissues is the major obstacle to photodynamic therapy (PDT). Herein, a self-oxygenating nanoplatform T4-Ce6-Cat (T4CCa) is used for improving PDT. T4 acts as a nanocarrier, with catalase (Cat) protein displayed on the capsid to trigger the hydrogen peroxide (H2O2) degradation. The number of displayed Cats can be precisely controlled by the feed concentration. Chemically coupled chlorin e6 (Ce6) is a photosensitizer to generate reactive oxygen species (ROS). By means of genetic engineering, phage display technology, and chemical modification, the T4CCa converts to "super tumor phage". The 852 Cat molecules, displayed on the phage surface, like a brush, increase the oxygen concentration to 21.7 mg/L in a short time (1 min), which effectively relieves tumor hypoxia. Adequate oxygen enables Ce6 to produce ROS effectively (93.6%), and the tumor inhibition rate reaches 86.07%. In vitro and in vivo toxicity assays reveal that T4CCa exhibits good biocompatibility at the molecular level, cellular level, and tissue organ level. More importantly, Cat still has a high catalytic capacity after T4CCa storage for a while. This work combines synthetic biology and nanotechnology to alleviate tumor hypoxia, providing a strategy for tumor treatment.