Photo‐Amplified Plasma Membrane Rupture by Membrane‐Anchoring NIR‐II Small Molecule Design for Improved Cancer Photoimmunotherapy

Immunotherapy is a promising cancer treatment method for eradicating tumor cells by enhancing the immune response. However, there are several major obstacles to conventional phototherapy-mediated immune responses, including inadequate immunogenicity and immunosuppressive environment. Here, we present a novel photoimmunotherapy modality-the development of membrane-anchoring small molecule inducing plasma membrane rupture (PMR) by NIR-II photo-stimulation, thus evoking cell necrotic death and enhancing antitumor immunotherapy. Our top-performing membrane-anchoring small molecule (CBT-3) exhibits temperature-tunable PMR efficiency, allowing rapid necrotic death in cancer cells at 50 μM dose by using exogenous NIR-II light-mediated mild photothermal effect (1064 nm, 0.6 W cm