Multifunctional Mesoporous Silicon Nanoparticles for MRI-Based Diagnostic Imaging and Glioma Therapy

作者：Huiru Zhu, Xiaoying Ni, Jiaxin Su, Yong Qin, Xiaoya He, Bo Liu, Shuang Ding, Haoru Wang, Xiangmin Zhang, Jie Huang, Qian Hu, Ruo-Fei Ma, Jinhua Cai · 发表于：ACS Applied Materials & Interfaces · 年份：2025 · DOI：10.1021/acsami.5c02882 · 被引用次数：7 · 研究领域：Nanoplatforms for cancer theranostics、Advanced Nanomaterials in Catalysis、Nanoparticle-Based Drug Delivery

To overcome the limited efficacy of chemodynamic therapy (CDT) caused by insufficient hydrogen peroxide (H 2 O 2 ) in the tumor microenvironment, we engineered a glutathione (GSH)-responsive multifunctional nanosystem, HCTG-C, based on hollow mesoporous organosilica nanoparticles. This system integrates tirapazamine (TPZ), glucose oxidase (GOx), in situ-synthesized copper sulfide (CuS), and CT2A glioma cell membrane coating to enable dual tumor-targeted therapy and self-imaging capabilities. The therapeutic mechanism relies on three synergistic cascades: (1) GOx-mediated glucose oxidation to deplete oxygen and generate H 2 O 2, establishing a self-sustaining H 2 O 2 supply; (2) GSH-triggered CuS conversion to Cu(I), amplifying Fenton-like reactions for efficient H 2 O 2 -to-reactive oxygen species conversion and ferroptosis induction; and (3) hypoxia-activated TPZ to exert cytotoxic effects, synergizing chemotherapy with CDT. Experimental results demonstrated that HCTG-C achieves real-time MRI monitoring via GSH depletion-driven Cu valence transitions, while its self-replenishing H 2 O 2 and oxygen-activation mechanisms significantly enhance antitumor efficacy against CT2A glioma in vitro and in vivo. By innovatively combining H 2 O 2 self-supply cascades, hypoxia-activated chemotherapy, and ferroptosis-driven CDT, this work presents a paradigm-shifting strategy for self-imaging-guided combinatorial therapy, advancing ferroptosis-based approaches for precision glioma treatmen...