Photoinduced Plasmon Electron Transfer-based Bioorthogonal Cleavage Reaction for Precision Tumor Therapy

Photocatalytic reactions have been harnessed to develop advanced medical solutions for transformative cancer therapy. However, their limited catalytic activities within biological environments must be enhanced to maximize their potential in practical applications. Here, a spatiotemporally controllable photocatalytic cancer therapy is reported through the photoinduced plasmon electron transfer (PiPET)-based biorthogonal cleavage reaction of a pro-photosensitizer, allyl carbamate-conjugated methylene blue (MB). The electron transfer in Pd-conjugated Au nanobipyramids is examined to improve catalytic activity by simulating the energy differences between the desorbed and adsorbed states, bond distances, and charge densities with and without excess electrons. A significantly enhanced release of allyl carbamate-conjugated methylene blue is achieved by ninefold and demonstrated precise spatiotemporal control of the bioorthogonal reaction in vivo. Both in vitro and in vivo studies reveal the remarkable tumor-suppressing capability of the bioorthogonal system, which is attributed to the photothermal and PiPET effects, coupled with the prevention of leuko-MB formation. The PiPET-based bioorthogonal cleavage reaction can offer an innovative solution for precise tumor therapy using spatiotemporal phototherapeutic strategies.