Photomodulation technology,characterized by its high spatiotemporal resolution,has emerged as a transformative approach for precise,rapid,and noninvasive regulation of intricate cellular signaling networks,offering un...Photomodulation technology,characterized by its high spatiotemporal resolution,has emerged as a transformative approach for precise,rapid,and noninvasive regulation of intricate cellular signaling networks,offering unprecedented opportunities for biomedical research.Nevertheless,the in vivo implementation of wireless photomodulation remains constrained by the inherent limitations of conventional photoresponsive systems.Addressing this challenge,we report a BODIPY-based photocatalyst with exceptional red-light responsiveness(λ>630 nm).Transient spectroscopic studies show that this photocatalyst exhibits the feature with solvent polarity-switching excited state dynamics.In addition,we observed ultralong triplet-state lifetimes(590μs in tetrahydrofuran;862μs in toluene),which is favorable for establishing a far-red-light-driven photocatalytic decaging platform that synergistically integrates the BODIPY photocatalyst with endogenous NADH as the intrinsic electron donor.Crucially,this system demonstrates robust in vivo efficacy,achieving significant tumor growth suppression in murine tumor models through localized prodrug activation.This work not only provides fundamental insights into engineering long-lived triplet states in metal-free organic photocatalysts but also pioneers a biocompatible strategy for spatiotemporally controlled therapeutic interventions,bridging the gap between advanced photochemistry and precision biomedicine.展开更多
Comprehensive Summary Pd-mediated bioorthogonal cleavage reactions have been extensively utilized in the activation of prodrug molecules,precise regulation of protein function,and cellular engineering.However,the avai...Comprehensive Summary Pd-mediated bioorthogonal cleavage reactions have been extensively utilized in the activation of prodrug molecules,precise regulation of protein function,and cellular engineering.However,the availability of cleavable"caging"groups is quite limited,and their application in nucleic acid modification has seldom been reported.Herein,we introduce a method based on Pd-catalyzed reduction amination of azides as a decaging strategy to activate the activity of biomolecules.We designed modifications on the bioactive sites with azides or their derivatives to mask the related biological function,followed by the release of biological activity through Pd-catalyzed NaBH4 reduction amination reaction.This study has demonstrated that the strategy can effectively be used to activate bioactive molecules such as fluorescent probes,prodrugs,and to regulate the biological function of RNA,including reverse transcription extension,binding to ligands,and cleavage activity of the CRISPR-Cas system.All results confirm that this strategy provides an efficient and controllable"OFF to ON"biological switch,capable of achieving significant regulatory effects substoichiometrically,and is expected to be extended to other biological applications.展开更多
基金supported by the National Natural Science Foundation of China(NSFC)(013398,22377063)the Research Start-Up Fund of Nankai University and the Haihe Laboratory of Sustainable Chemical Transformations(24HHWCSS00020)。
文摘Photomodulation technology,characterized by its high spatiotemporal resolution,has emerged as a transformative approach for precise,rapid,and noninvasive regulation of intricate cellular signaling networks,offering unprecedented opportunities for biomedical research.Nevertheless,the in vivo implementation of wireless photomodulation remains constrained by the inherent limitations of conventional photoresponsive systems.Addressing this challenge,we report a BODIPY-based photocatalyst with exceptional red-light responsiveness(λ>630 nm).Transient spectroscopic studies show that this photocatalyst exhibits the feature with solvent polarity-switching excited state dynamics.In addition,we observed ultralong triplet-state lifetimes(590μs in tetrahydrofuran;862μs in toluene),which is favorable for establishing a far-red-light-driven photocatalytic decaging platform that synergistically integrates the BODIPY photocatalyst with endogenous NADH as the intrinsic electron donor.Crucially,this system demonstrates robust in vivo efficacy,achieving significant tumor growth suppression in murine tumor models through localized prodrug activation.This work not only provides fundamental insights into engineering long-lived triplet states in metal-free organic photocatalysts but also pioneers a biocompatible strategy for spatiotemporally controlled therapeutic interventions,bridging the gap between advanced photochemistry and precision biomedicine.
基金the National Natural Science Foundation of China(Nos.22177089,21721005,92153303,22037004,22177088)the Fundamental Research Funds for the Central Universities(2042021kf0211)Translational Medicine and Interdisciplinary Research Joint Fund of Zhongnan Hospital of Wuhan University(Grant No.ZNJC202309).
文摘Comprehensive Summary Pd-mediated bioorthogonal cleavage reactions have been extensively utilized in the activation of prodrug molecules,precise regulation of protein function,and cellular engineering.However,the availability of cleavable"caging"groups is quite limited,and their application in nucleic acid modification has seldom been reported.Herein,we introduce a method based on Pd-catalyzed reduction amination of azides as a decaging strategy to activate the activity of biomolecules.We designed modifications on the bioactive sites with azides or their derivatives to mask the related biological function,followed by the release of biological activity through Pd-catalyzed NaBH4 reduction amination reaction.This study has demonstrated that the strategy can effectively be used to activate bioactive molecules such as fluorescent probes,prodrugs,and to regulate the biological function of RNA,including reverse transcription extension,binding to ligands,and cleavage activity of the CRISPR-Cas system.All results confirm that this strategy provides an efficient and controllable"OFF to ON"biological switch,capable of achieving significant regulatory effects substoichiometrically,and is expected to be extended to other biological applications.
