Biomarker‐Gated Photocatalysis Uncaging in Live System
Abstract
Abstract Spatiotemporal precision in photocontrolled biochemical reactions remains a central challenge. We report a sequential activation platform that integrates biomarker‐triggered unlocking of photocatalyst activity with photocatalytic bioorthogonal uncaging, designed to enhance bioimaging and enable AND‐gate therapeutics. By engineering diiodo‐BODIPY carboxylic acid—an organic photocatalyst enabling efficient azide‐to‐amine reduction under light—we masked its carboxyl group as an ester to completely suppress photocatalytic activity. Strategic incorporation of enzyme‐ or ROS‐cleavable self‐immolative linkers restored catalysis in response to nitroreductase (NTR) or H 2 O 2 , respectively. This “lock‐and‐key” mechanism enables two primary functionalities: enhanced bioimaging through signal amplification by biomarker‐activated BODIPY catalysts, and an “AND‐gate” therapeutic activation requiring both NTR presence and light exposure for the release of caged therapeutic agents like RNase A or doxorubicin. Our platform integrates bioresponsive chemistry with light‐mediated control, offering a blueprint for logical gate‐regulated cellular processes and advancing precision medicine with potential for more targeted and efficient therapies.
Article Details
Authors (10)
Guoming Tong
Key Laboratory of Chemical Biology & Traditional Chinese Medicine Research of Ministry of Education, Key Laboratory of Phytochemical R&D of Hunan Province, College of Chemistry and Chemical Engineering Hunan Normal University Changsha Hunan 410081 China
Changfeng Li
Key Laboratory of Chemical Biology & Traditional Chinese Medicine Research, Ministry of Education, Institute of Interdisciplinary Studies, College of Chemistry and Chemical Engineering
Qing Zhou
Fang Wang
Wei He
Erhu Xiong
Key Laboratory of Chemical Biology & Traditional Chinese Medicine Research, Ministry of Education, Institute of Interdisciplinary Studies, College of Chemistry and Chemical Engineering
Lebin Su
Sheng Yang
Key Laboratory of Chemical Biology & Traditional Chinese Medicine Research, Ministry of Education, Institute of Interdisciplinary Studies, College of Chemistry and Chemical Engineering
Guhuan Liu
State Key Laboratory of Precision and Intelligent Chemistry, Department of Polymer Science and Engineering, School of Chemistry and Materials Science
Ronghua Yang
Key Laboratory of Chemical Biology & Traditional Chinese Medicine Research, Ministry of Education, Institute of Interdisciplinary Studies, College of Chemistry and Chemical Engineering