Reactive Oxygen Species‐Responsive Biomimetic Nanoplatelets for Thrombus‐Mediated Photothermal Immunotherapy of Tumor

One of the biggest advantages of photothermal therapy (PTT) as a compelling cancer treatment is its spatiotemporal nature. However, there are still significant challenges in completely eradicating tumors through PTT due to the unclear boundary between tumor and normal tissues. Here, we present a tumor vascular disruption strategy that leverages photothermally induced hemorrhage to enhance therapeutic efficacy through thrombosis-driven intensive PTT and peripheral tumor vascular embolization. A biomimetic nanoplatelet (PPIE@P), reactive oxygen species (ROS)-responsive nanogel scaffold loading with indocyanine green (ICG) and the coagulant etamsylate with platelet membrane camouflage, is developed. Upon near-infrared (NIR) irradiation, ICG-generated ROS trigger precise disintegration of PPIE@P, releasing the coagulant while producing hyperthermia that induces vascular injury and hemorrhage. This process activates the coagulation cascade and recruits additional nanoplatelets to the hemorrhagic tumor site. Subsequently, the penetrating ICG and coagulant-accelerated blood clots enable intense hyperthermia during a second photoirradiation, whereas embolization of peripheral tumor-associated vessels contributes to complete tumor eradication. Notably, this antiangiogenic PTT strategy also elicits a potent systematic immune response by promoting dendritic cell maturation and effector T-cell infiltration. Overall, this work introduces a thrombus-augmented PTT paradigm with strong potential for future clinical translation.