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<p>Extracellular vesicles (EVs) hold great potential as a therapeutic delivery system for cancer treatment. Here, we develop an innovative targeted drug delivery platform, human leukocyte antigen-G-VHH antibody-modified EV (α-HLA-G-EV), to enhance therapeutic efficacy. A genetically engineered HEK293T stable clone is utilized to produce α-HLA-G-EV, which are subsequently loaded with chemotherapeutic agents to create HLA-G-targeting drug-loaded EVs (drug@α-HLA-G-EV). The cytotoxicity of drug@α-HLA-G-EV is assessed in various cancer cell lines, demonstrating superior tumor targeting and therapeutic efficacy compared to standard chemotherapies. In vivo experiments using xenograft NPG mouse models, established with MDA-MB-231 and U87 cell lines, further confirm the enhanced antitumor activity of Doxorubicin@α-HLA-G-EV and Temozolomide@α-HLA-G-EV. These findings are consistent with results observed in patient-derived breast cancer and GBM cell models. Additionally, drug@α-HLA-G-EV causes far less damage to normal organs than Lipo-Dox. These findings highlight the potential of α-HLA-G-EV as a versatile platform for precise and efficient cancer treatment.</p>

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Engineering HLA-G-targeted extracellular vesicles nanoplatform for enhanced cancer therapy through precise cancer drug delivery

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月13日

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  • Ming-You Shie,
  • Shi-Wei Huang,
  • Yeh Chen,
  • Mei-Chih Chen,
  • Chih-Ming Pan,
  • Cheng-Yu Chen,
  • Yen-Hong Lin,
  • Min-Hua Yu,
  • Kai-Wen Kan,
  • Shao-Chih Chiu,
  • Hui-Chun Ho,
  • Yi-Wen Chen,
  • Der-Yang Cho

摘要

Extracellular vesicles (EVs) hold great potential as a therapeutic delivery system for cancer treatment. Here, we develop an innovative targeted drug delivery platform, human leukocyte antigen-G-VHH antibody-modified EV (α-HLA-G-EV), to enhance therapeutic efficacy. A genetically engineered HEK293T stable clone is utilized to produce α-HLA-G-EV, which are subsequently loaded with chemotherapeutic agents to create HLA-G-targeting drug-loaded EVs (drug@α-HLA-G-EV). The cytotoxicity of drug@α-HLA-G-EV is assessed in various cancer cell lines, demonstrating superior tumor targeting and therapeutic efficacy compared to standard chemotherapies. In vivo experiments using xenograft NPG mouse models, established with MDA-MB-231 and U87 cell lines, further confirm the enhanced antitumor activity of Doxorubicin@α-HLA-G-EV and Temozolomide@α-HLA-G-EV. These findings are consistent with results observed in patient-derived breast cancer and GBM cell models. Additionally, drug@α-HLA-G-EV causes far less damage to normal organs than Lipo-Dox. These findings highlight the potential of α-HLA-G-EV as a versatile platform for precise and efficient cancer treatment.