A detoxified exosome–ECM hydrogel depot for localized and sustained chemotherapy in prostate cancer

作者：Guangfeng Zhu, Yansheng Su, Younes Pilehvar, Zhina Liu, Chen Ma, Anan Li, Lele Hui, Yong Chen · 发表于：Journal of Biological Engineering · 年份：2026 · DOI：10.1186/s13036-026-00623-2 · 被引用次数：3 · 研究领域：Extracellular vesicles in disease、Cancer, Lipids, and Metabolism、Toxin Mechanisms and Immunotoxins

Advanced prostate cancer often necessitates chemotherapy, yet conventional agents such as doxorubicin (DOX) suffer from poor tumor specificity, systemic toxicity, and acquired resistance. Here, we report a biomimetic, injectable hydrogel depot that integrates enzyme-detoxified tumor exosomes (Detox-EXOs) with a chitosan–decellularized prostate extracellular matrix (CS–dpECM) scaffold for localized and sustained chemotherapy. The Detox-EXOs, generated by enzymatic removal of oncogenic and immunogenic contents while preserving membrane integrins and targeting ligands, function as safe, tumor-homing nanocapsules for DOX encapsulation. Embedded within the CS–dpECM matrix, these vesicles form a prostate-specific depot capable of controlled release and tissue-directed drug retention. Rheological characterization revealed a stable, elastic hydrogel network (G′ ≈ 0.8 kPa, low tan δ) with shear-thinning injectability. Release studies demonstrated sustained DOX elution over 14 days (~ 80% cumulative), with DOX@EXOs exhibiting slower release than free DOX. Both blank hydrogels and detoxified EXOs alone were biocompatible, showing negligible cytotoxicity. In AT-3 prostate cancer cells, confocal microscopy confirmed efficient intracellular DOX uptake co-localized with exosomal markers, leading to pronounced apoptosis (~ 77% Annexin-positive) and significant downregulation of Ki-67 and Cyclin D1 expression. Collectively, these findings demonstrate that the DOX@EXOs/CS–dpECM hydrogel depot ...