The feast of prisoners: Confining drugs and inflammatory factors locally in tumors.

Cancer metastasis remains the leading cause of cancer-related mortality. However, conventional ablation therapies such as photothermal/photodynamic therapy (PTT/PDT) may paradoxically exacerbate metastatic spread by inducing vascular disruption, fibrinolytic activation, and leakage of inflammatory chemokines. To address this challenge, we developed a novel "LOCK" therapy (Light-triggered Occlusion Combined with Key antifibrinolytics), which combines PTT/PDT with the antifibrinolytic agent tranexamic acid (TXA) to stabilize tumor-associated microthrombi and achieve sustained vascular occlusion. This strategy not only enhances primary tumor eradication but also suppresses systemic dissemination by entrapping tumor cells and inflammatory mediators within the tumor microenvironment. More importantly, this approach significantly improved the intratumoral retention of chemotherapeutic agents while reducing their redistribution. Furthermore, we engineered a biomimetic near-infrared (NIR)-activated nanoplatform, IR780/TXA TRN@PM, co-loaded with IR780 and TXA and coated with platelet membrane (PM) for targeted delivery to tumor and hemorrhage sites. In murine models of breast cancer and melanoma, the LOCK strategy significantly inhibited primary tumor growth and metastasis, enhanced intratumoral retention of chemotherapeutic agents such as doxorubicin, and reshaped the immunosuppressive microenvironment. These findings support the translational potential of a mechanism-based combination strategy that converts a pathological response into a therapeutic advantage, providing a broadly applicable approach to overcome the limitations of conventional ablation therapies.