Diagnostic and Therapeutic Integration Prodrug: Dynamic Probe Engineering via Cys/GSH Depletion to Amplify Type I Photodynamic Therapy for Breast Cancer
Cancer is a serious threat to human health, and it is essential to find effective methods for detecting and treating cancer. Diagnostic integration is a new strategy for cancer diagnosis and treatment that enables localized detection and treatment of tumors in a single administration and effectively reduces the toxic side effects on normal tissues. It remains a challenge for small-molecule probes to achieve multifunctionality in sensing, targeting, imaging, and therapy. Photodynamic therapy (PDT), which uses photosensitizers to generate reactive oxygen species under specific wavelengths of light to ablate tumor tissue, has demonstrated unique advantages in tumor treatment. However, the high expression of Cys/GSH in the tumor region will consume the reactive oxygen species generated by photosensitizers during PDT and reduce the therapeutic effect of the tumor. In this study, the highly expressed Cys/GSH in the tumor microenvironment was used as the activation source, and benzopyrylium salt and coumarin dyes were selected as fluorophores, with the ether bond and aldehyde group as recognition sites, to construct a near-infrared-activated Cys/GSH fluorescent probe (Bpl-O-Cou). Based on the intramolecular rearrangement mechanism and intramolecular cyclization mechanism, Bpl-O-Cou could discriminate the detection of Cys/GSH accompanied by different fluorescence emissions. Under near-infrared laser irradiation, Bpl-O-Cou + Cys/GSH could produce •OH and O2–•, leading to 4T1 cell death. In vivo experiments further illustrated the interventional role of Bpl-O-Cou in the PDT process. This study provides a new idea for the design of multifunctional probes for cancer diagnostics and therapeutics.
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