A Biocompatible Heterogeneous MOF-Cu Catalyst for In Vivo Drug Synthesis in Targeted Subcellular Organelles.
As a typical bioorthogonal reaction, the copper-catalyzed azide-alkyne cycloaddition (CuAAC) has been used for drug design and synthesis. However, for localized drug synthesis, it is important to be able to determine where the CuAAC reaction occurs in living cells. In this study, we constructed a heterogeneous copper catalyst on a metal-organic framework that could preferentially accumulate in the mitochondria of living cells. Our system enabled the localized synthesis of drugs through a site-specific CuAAC reaction in mitochondria with good biocompatibility. Importantly, the subcellular catalytic process for localized drug synthesis avoided the problems of the delivery and distribution of toxic molecules. In vivo tumor therapy experiments indicated that the localized synthesis of resveratrol-derived drugs led to greater antitumor efficacy and minimized side effects usually associated with drug delivery and distribution.
['Wang|Faming|F|', 'Zhang|Yan|Y|', 'Liu|Zhengwei|Z|', 'Du|Zhi|Z|', 'Zhang|Lu|L|', 'Ren|Jinsong|J|', 'Qu|Xiaogang|X|0000-0003-2868-3205']
D000480:Alkynes D000818:Animals D000975:Antioxidants D001386:Azides D017173:Caenorhabditis elegans D002384:Catalysis D049109:Cell Proliferation D057930:Click Chemistry D003300:Copper D061565:Cycloaddition Reaction D006801:Humans D061986:MCF-7 Cells D000073396:Metal-Organic Frameworks D051379:Mice D008928:Mitochondria D000077185:Resveratrol
drug synthesis subcellular organelles bioorthogonal chemistry click chemistry heterogeneous catalysis