Yubin Chen,Yao Lu,Kai Hua,Junyan Li,Jingtao Zheng,Yanyan Pan,Yongzhong Du,Qiang Zhang,Weishuo Li
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Intracellular Generation of Alkyl Radicals Enabled by a Self-Catalytic ATRP Nanoinitiator.
Oxygen-independent alkyl radicals (R•) have demonstrated great promise in combating tumor hypoxia. Currently, Azo compounds have been the primary source of R•, suffering from external stimuli and decomposition during circulation. Herein, we developed a self-catalytic ATRP nanoinitiator that could generate R• via glutathione (GSH) reduction and thus selectively induce apoptosis of tumor cells. Specifically, a conjugation of laccase (possessing a copper(II) complex) and polymeric alkyl bromide, poly(iBBr), was fabricated to yield an ATRP nanoinitiator (Lac-P(iBBr)). After internalization by cells featured with overexpressed GSH, copper(II) in Lac-P(iBBr) was reduced to copper(I) by GSH, which abstracted the Br atom in poly(iBBr) to yield toxic R•. Moreover, GSH-depletion intensified the oxidative damage caused by R•. Efficient generation of R• by Lac-P(iBBr) could happen in lab flasks, living cells, and tumor-bearing mice without any external stimuli, as demonstrated by the radical product, as well as the consumption of GSH. Moreover, the self-catalytic ATRP nanoinitiator significantly induced cell apoptosis and suppressed tumor growth. Our study expands the chemical toolbox to manipulate cell fates.
期刊介绍:
ACS Macro Letters publishes research in all areas of contemporary soft matter science in which macromolecules play a key role, including nanotechnology, self-assembly, supramolecular chemistry, biomaterials, energy generation and storage, and renewable/sustainable materials. Submissions to ACS Macro Letters should justify clearly the rapid disclosure of the key elements of the study. The scope of the journal includes high-impact research of broad interest in all areas of polymer science and engineering, including cross-disciplinary research that interfaces with polymer science.
With the launch of ACS Macro Letters, all Communications that were formerly published in Macromolecules and Biomacromolecules will be published as Letters in ACS Macro Letters.