T4 Phage Display Technology for Enhanced Photodynamic Therapy of Breast Cancer

Hypoxiain tumor tissues is the major obstacle to photodynamictherapy (PDT). Herein, a self-oxygenating nanoplatform T4-Ce6-Cat(T4CCa) is used for improving PDT. T4 acts as a nanocarrier, withcatalase (Cat) protein displayed on the capsid to trigger the hydrogenperoxide (H2O2) degradation. The number of displayedCats can be precisely controlled by the feed concentration. Chemicallycoupled chlorin e6 (Ce6) is a photosensitizer to generate reactiveoxygen species (ROS). By means of genetic engineering, phage displaytechnology, and chemical modification, the T4CCa converts to "supertumor phage". The 852 Cat molecules, displayed on the phagesurface, like a brush, increase the oxygen concentration to 21.7 mg/Lin a short time (1 min), which effectively relieves tumor hypoxia.Adequate oxygen enables Ce6 to produce ROS effectively (93.6%), andthe tumor inhibition rate reaches 86.07%. In vitro and in vivo toxicity assays reveal that T4CCa exhibitsgood biocompatibility at the molecular level, cellular level, andtissue organ level. More importantly, Cat still has a high catalyticcapacity after T4CCa storage for a while. This work combines syntheticbiology and nanotechnology to alleviate tumor hypoxia, providing astrategy for tumor treatment.