Reversible Deactivation Radical Polymerization In, On, and Around Living Cells

Abstract Reversible deactivation radical polymerization (RDRP) enables the synthesis of well-defined polymers under mild, cytocompatible conditions. Here we examine recent advances in RDRP performed inside living cells, on cell surfaces, and in the extracellular environment. Intracellular polymerizations exploit endogenous reducing species and biomarker-responsive photocatalysts to generate polymers for cell tracking, drug retention, and modulation of cellular functions. Cell−surface polymerizations employ physical association, covalent anchoring, and grafting-from strategies to construct interfaces modulating cell recognition, aggregation, and catalytic activity. Extracellular approaches exploit cellular metabolism and electron-transfer pathways to regulate ATRP and RAFT processes, while cytocompatible polymerizations provide routes to synthetic extracellular matrices and hydrogels. Across these settings, the biological environment can actively participate in controlling radical generation, catalyst activation, and polymer localization. We discuss the opportunities and remaining challenges of these strategies and highlight how integrating polymer chemistry with cellular metabolism and spatiotemporal control could enable biologically responsive polymerization systems.