Scholarlink

<p>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&#xa0;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 enables targeted, sustained, and biocompatible chemotherapeutic delivery in vitro. This work presents a proof-of-concept hybrid system combining detoxified exosomal nanocarriers with an organ-specific ECM hydrogel, supporting further preclinical development toward localized precision therapy for prostate cancer.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年1月22日

查看全文
  • Guangfeng Zhu,
  • Yansheng Su,
  • Younes Pilehvar,
  • Zhina Liu,
  • Chen Ma,
  • Anan Li,
  • Lele Hui,
  • Yong Chen

摘要

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 enables targeted, sustained, and biocompatible chemotherapeutic delivery in vitro. This work presents a proof-of-concept hybrid system combining detoxified exosomal nanocarriers with an organ-specific ECM hydrogel, supporting further preclinical development toward localized precision therapy for prostate cancer.