Spatiotemporally Controlled Prodrug Release From Light-Triggered Azo-Bond-Cleaved BODIPY Nanoplatform for Trimodal Synergistic Ovarian Cancer Therapy.

Wang, Jiaqi; Zhang, Jie; Xu, Dongping; Zhang, Yiming; Xia, Xueqing; Li, Shuo; Jiang, Xin-Dong; Fan, Jiangli et al. · Adv Healthc Mater · 2026

basic_science · Level V

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Abstract

Chemotherapy (CT) suffers from poor selectivity and systemic toxicity, while photodynamic therapy (PDT) and photothermal therapy (PTT) are inherently limited by tumor hypoxia and thermoresistance. Herein, we develop a trimodal synergistic nanoplatform (PDM-BDP NPs) for ovarian cancer treatment by integrating PDT, mild PTT (mPTT), and CT into a single azo-bond-linked prodrug system. Upon 808 nm laser irradiation, PDM-BDP NPs generate reactive oxygen species and mild hyperthermia, while simultaneously triggering azo-bond cleavage to release the chemotherapeutic agent phenylenediamine mustard (PDM) and transform into NH<sub>2</sub>-BDP, which retains photothermal activity for sustained thermal output. PDM-BDP NPs exhibit efficient cellular uptake, predominant mitochondrial co-localization, and potent photocytotoxicity against A2780 cells with low dark toxicity. Transcriptomics reveals multi-target reprogramming involving proteotoxic stress, DNA damage, and TNF/MAPK activation. Laser-activated PDM-BDP NPs achieve subtotal tumor ablation with excellent biocompatibility. This trimodal synergistic strategy provides a promising approach for precise ovarian cancer therapy.