journal article·2025-07-15

A Nitroreductase-Responsive Type I Photosensitizer with Aggregation-Induced Emission Characteristics for Precise Hypoxic Cancer Theranostics

Kristy W. K. Lam, Yaojia Zhang, Wutong Du, Jie Sun, Feiyi Sun, Yuyang Chen, Charlie C. H. Ma, Jacky W. Y. Lam, Ryan T. K. Kwok, Jianwei Sun, Xuewen He, Ben Zhong Tang

ACS Nano· Volume 19· Issue 27
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Abstract

Cancer remains a significant global health challenge, with early and accurate detection being key to improving treatment outcomes. Developing targeted photosensitizers (PS) that selectively image and treat cancer cells is critical for cancer diagnosis, staging, and treatment monitoring. Understanding the hypoxic nature of solid tumors is essential in cancer detection, as hypoxia is associated with tumor aggressiveness and therapy resistance. Nitroreductase (NTR), which is overexpressed in hypoxic tumors, offers a target for selective imaging and treatment. In this study, we developed a type-I PS called TPAPyN, which is responsive to NTR. TPAPyN facilitates the imaging of hypoxic cancer cells and facilitates image-guided photodynamic therapy (PDT). Because of photoinduced electron transfer, TPAPyN does not emit fluorescence in the aqueous environment. However, its fluorescence is restored when NTR cleaves the nitrofuran quencher, forming highly emissive TPAPy aggregates. This characteristic makes TPAPyN a valuable fluorescent probe for specific imaging of NTR-overexpressed cancer cells. Additionally, TPAPy exhibits high efficiency in generating reactive oxygen species, indicating its potential as a PS for cancer treatment via PDT.
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Research context

OpenAlex topics: Nanoplatforms for cancer theranostics · Luminescence and Fluorescent Materials · Advanced biosensing and bioanalysis techniques

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Chemistry, Department of Chemical and Biological Engineering, Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction, and State Key Laboratory of Nervous System Disorders, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong 999077, China

The Key Lab of Health Chemistry and Molecular Diagnosis of Suzhou, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, 199 Ren’ai Road, Suzhou, Jiangsu 215123, China

Ph.D.Department of Comprehensive Basic Experiment

The Ninth Medical Center. of Chinese PLA General Hospital

Institute of Infectious Diseases

Shenzhen Bay Laboratory

HKUST-Shenzhen Research Institute, No. 9 Yuexing first RD, South Area Hi-Tech Park, Nanshan, Shenzhen 518057, China

School of Science and Engineering, Shenzhen Institute of Aggregate Science and Technology

The Chinese University of Hong Kong, Shenzhen

Funding

Research Grants Council, University Grants Committee · Science, Technology and Innovation Commission of Shenzhen Municipality · Innovation and Technology Commission · Shenzhen Key Laboratory of Functional Aggregate Material

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