Hypoxia‐Responsive Hydrogen‐Bonded Organic Framework‐Mediated Protein Delivery for Cancer Therapy

作者：He Xu, Jian Wang, Xiao Liu, Qingyu Niu, Zhiqiang Li, Banglin Chen, Qingqing Xiong · 发表于：Advanced Healthcare Materials · 年份：2024 · DOI：10.1002/adhm.202400747 · 被引用次数：19 · 研究领域：Metal-Organic Frameworks: Synthesis and Applications、Nanoplatforms for cancer theranostics、Supramolecular Self-Assembly in Materials

The efficient delivery of therapeutic proteins to tumor sites is a promising cancer treatment modality. Hydrogen-bonded organic frameworks (HOFs) are successfully used for the protective encapsulation of proteins; however, easy precipitation and lack of controlled release of existing HOFs limit their further application for protein delivery in vivo. Here, a hypoxia-responsive HOF, self-assembled from azobenzenedicarboxylate/polyethylene glycol-conjugated azobenzenedicarboxylate and tetrakis(4-amidiniumphenyl)methane through charge-assisted hydrogen-bonding, is developed for systemic protein delivery to tumor cells. The newly generated HOF platform efficiently encapsulates representative cytochrome C, demonstrating good dispersibility under physiological conditions. Moreover, it can respond to overexpressed reductases in the cytoplasm under hypoxic conditions, inducing fast intracellular protein release to exert therapeutic effects. The strategy presented herein can be applied to other therapeutic proteins and can be expanded to encompass more intrinsic tumor microenvironment stimuli. This offers a novel avenue for utilizing HOFs in protein-based cancer therapy.