Tumor Microenvironment‐Triggered Intelligent Nanoassemblies for Fluorescence Imaging Activation and Tumor‐Specific Embolization Therapy Amplification

Abstract Tumor microenvironment (TME)‐responsive nanoparticles have garnered significant attention in the biomedical field due to their tumor‐specific properties, which enable precise drug‐controlled release for enhanced therapeutic efficacy and markedly improved safety in the in vivo application of anticancer drugs. Herein, a self‐assembled nanoparticle ICT, capable of intelligently controlling thrombin release, is fabricated via a facile one‐step assembly of thrombin, iron sucrose, and the photosensitizer Chlorin e6 (Ce6), followed by surface modification with DSPE‐mPEG‐cRGD to enhance tumor‐targeting capability. The as‐synthesized smart nanoassembly exhibits inherent fluorescence quenching, but its fluorescence imaging properties can be rapidly restored under the weakly acidic and glutathione (GSH)‐overexpressed tumor microenvironment. Upon cellular internalization, the ICT nanoparticles are promptly degraded in the tumor microenvironment, releasing thrombin to induce rapid tumor vessel embolization. Concurrently, the liberated iron sucrose elevates hemoglobin levels in vivo, amplifying the embolization effect, while the generated Fe ²⁺ delivers a lethal blow to tumor cells through chemodynamic therapy and modulates the tumor immune microenvironment. The ICT nanoparticles not only achieve safe in vivo delivery of thrombin but also establish a multifunctional nanotheranostic system for tumor treatment via tumor‐specific fluorescence imaging.