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Porphyrin-based-MOF nanocomposite hydrogels for synergistic sonodynamic and gas therapy against tumor
Yunqi Kuang1, Ziwen Zhang1, Kai Zhu2
1School of Chemistry and Chemical Engineering, Shanghai Frontiers Science Research Center for Druggability of Cardiovascular noncoding RNA, Shanghai Engineering Technology Research Center for Pharmaceutical Intelligent Equipment, Institute for Frontier Medical Technology, Shanghai University of Engineering Science, Shanghai 201620, China; Department of emergency and critical care medicine, Shanghai Pudong New Area People's Hospital, China.
Abstract:
The glioma is one of the most aggressive tumors in humans, which is difficult to eradicate clinically. Therefore, we devised a porphyrin-based metal-organic frameworks (MOFs) crosslinking hyaluronic acid (HA) hydrogel nanocomposite through double-network (Cu-MOF-S-S-HA-Gel, CSSH-Gel), which is tumor responsive for enhanced gas therapy and sonodynamic therapy (SDT). Firstly, the hydrogels show extraordinary injectability and biocompatibility, which enables intratumor administration to circumvent the danger associated with surgery. The Cu-MOF-Cys and HA-Cys are interconnected through ether and disulfide bonds to establish a dual-network gel structure. The overexpressed glutathione (GSH) in tumor microenvironment (TME) reacts with disulfide bonds to release of the nanosensitizer (Cu-MOF). Subsequently, Cu-MOF generates reactive oxygen species (ROS) upon ultrasound irradiation for SDT, and releases L-cysteine(L-Cys) catalyzed by 3-mercapto pyruvate sulfotransferase (3-MST) to generate H2S for gas therapy. The CSSH-Gel obtained excellent synergistic anti-tumor effects (82.34 % inhibition ratio in vivo), which holds tremendous promise for the advancement of minimally invasive glioma therapies.
