ABSTRACT Reversible stimuli‐responsive materials offer unique opportunities for spatiotemporally precise modulation of biological systems. Here, we report a donor–π–acceptor azobenzene‐based aggregation‐induced emission luminogen, MTTBN, as a light‐responsive molecular tool capable of regulating the mechanical properties of tumor cell membranes under ultraviolet (UV) irradiation or inducing immunogenic cell death under 520 nm laser irradiation. UV‐triggered isomerization modulates membrane tension and intracellular trafficking, while 520 nm irradiation activates phototherapeutic effects to induce pyroptosis and antitumor immunity. In a bilateral tumor model, MTTBN‐mediated phototherapy at 520 nm not only markedly suppresses primary tumor growth but also elicits systemic antitumor immunity, inhibiting distant tumors and promoting robust immune memory, while maintaining controlled immune activation without detectable off‐target tissue damage. MTTBN, as a reversible and spatiotemporally controllable molecular platform, inspires future efforts to integrate precise photoregulation of membrane mechanics, efficient photothermal/photodynamic effects, and systemic immunomodulatory functions by employing two‐photon excitation or other nonlinear optical strategies to match the absorption of azobenzene derivatives with that of phototheranostic agents.
Wang et al. (Sun,) studied this question.