{"title":"Bio-Photo Dual Action of Intracellular Radical Polymerization","authors":"Chunxiao Wu, , , Ze Wei, , , Changfeng Li, , , Sheng Yang, , , Guhuan Liu*, , and , Ronghua Yang, ","doi":"10.1021/jacs.5c10871","DOIUrl":null,"url":null,"abstract":"<p >Achieving spatiotemporal control over intracellular polymerization presents a fundamental challenge in merging synthetic chemistry with living systems. Here, we introduce a stimuli-responsive photocatalyst strategy that enables biomarker- and light-gated radical polymerization within cells. Engineered 3,4,5,6-tetrabromofluorescein (TBF) photocatalysts incorporate protecting groups─responsive to endogenous reactive oxygen/sulfur species (ROS/RSS) or enzymes─that suppress photoinduced electron/energy transfer-reversible addition–fragmentation chain transfer (PET-RAFT) activity until simultaneous biomarker activation and irradiation occur. This AND-gated mechanism confines polymerization exclusively to target cells. Leveraging monomer design and this dual-control paradigm, <i>in situ</i> polymer growth selectively disrupts endoplasmic reticulum (ER) integrity, triggering ER stress, calcium release, and paraptosis─a caspase-independent cell death pathway characterized by cytoplasmic vacuolization and ER dilation. This platform establishes a versatile chemical approach for precision organelle intervention, advancing therapeutic discovery and synthetic biology applications.</p>","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"147 39","pages":"35604–35615"},"PeriodicalIF":15.6000,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of the American Chemical Society","FirstCategoryId":"92","ListUrlMain":"https://pubs.acs.org/doi/10.1021/jacs.5c10871","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
Abstract
Achieving spatiotemporal control over intracellular polymerization presents a fundamental challenge in merging synthetic chemistry with living systems. Here, we introduce a stimuli-responsive photocatalyst strategy that enables biomarker- and light-gated radical polymerization within cells. Engineered 3,4,5,6-tetrabromofluorescein (TBF) photocatalysts incorporate protecting groups─responsive to endogenous reactive oxygen/sulfur species (ROS/RSS) or enzymes─that suppress photoinduced electron/energy transfer-reversible addition–fragmentation chain transfer (PET-RAFT) activity until simultaneous biomarker activation and irradiation occur. This AND-gated mechanism confines polymerization exclusively to target cells. Leveraging monomer design and this dual-control paradigm, in situ polymer growth selectively disrupts endoplasmic reticulum (ER) integrity, triggering ER stress, calcium release, and paraptosis─a caspase-independent cell death pathway characterized by cytoplasmic vacuolization and ER dilation. This platform establishes a versatile chemical approach for precision organelle intervention, advancing therapeutic discovery and synthetic biology applications.
期刊介绍：
The flagship journal of the American Chemical Society, known as the Journal of the American Chemical Society (JACS), has been a prestigious publication since its establishment in 1879. It holds a preeminent position in the field of chemistry and related interdisciplinary sciences. JACS is committed to disseminating cutting-edge research papers, covering a wide range of topics, and encompasses approximately 19,000 pages of Articles, Communications, and Perspectives annually. With a weekly publication frequency, JACS plays a vital role in advancing the field of chemistry by providing essential research.
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