In Situ Polymerized Hollow Mesoporous Organosilica Biocatalysis Nanoreactor for Enhancing ROS-Mediated Anticancer Therapy

The combination of reactive oxygen species (ROS)-involved photodynamic therapy (PDT) and chemodynamic therapy (CDT) holds great promise for enhancing ROS-mediated cancer treatment. Herein, an in situ polymerized hollow mesoporous organosilica nanoparticle (HMON) biocatalysis nanoreactor is reported to integrate the synergistic effect of PDT/CDT for enhancing ROS-mediated pancreatic ductal adenocarcinoma treatment. 2-(1-hexyloxyethyl)-2-devinylpyropheophorbide-a photosensitizer is hybridized within the framework of HMON via an “in situ framework growth” approach. Then, the hollow cavity of HMONs is exploited as a nanoreactor for “in situ polymerization” to synthesize the polymer containing thiol groups, thereby enabling the immobilization of ultrasmall gold nanoparticles, which behave like glucose oxidase-like nanozyme, converting glucose into H₂O₂ to provide self-supplied H₂O₂ for CDT. Meanwhile, Cu²⁺-tannic acid complexes are further deposited on the surface of HMONs (HMON-Au@Cu-TA) to initiate Fenton-like reaction to covert the self-supplied H₂O₂ into •OH, a highly toxic ROS. Finally, collagenase (Col), which can degrade the collagen I fiber in the extracellular matrix, is loaded into HMON-Au@Cu-TA to enhance the penetration of HMONs and O₂ infiltration for enhanced PDT. This study provides a good paradigm for enhancing ROS-mediated antitumor efficacy. Meanwhile, this research offers a new method to broaden the application of silica based nanotheranostics.