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Engineering HLA-G-targeted extracellular vesicles nanoplatform for enhanced cancer therapy through precise cancer drug delivery #MMPMID41390497
Shie MY; Huang SW; Chen Y; Chen MC; Pan CM; Chen CY; Lin YH; Yu MH; Kan KW; Chiu SC; Ho HC; Chen YW; Cho DY
Nat Commun 2025[Dec]; ? (?): ? PMID41390497show ga
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 (alpha-HLA-G-EV), to enhance therapeutic efficacy. A genetically engineered HEK293T stable clone is utilized to produce alpha-HLA-G-EV, which are subsequently loaded with chemotherapeutic agents to create HLA-G-targeting drug-loaded EVs (drug@alpha-HLA-G-EV). The cytotoxicity of drug@alpha-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@alpha-HLA-G-EV and Temozolomide@alpha-HLA-G-EV. These findings are consistent with results observed in patient-derived breast cancer and GBM cell models. Additionally, drug@alpha-HLA-G-EV causes far less damage to normal organs than Lipo-Dox. These findings highlight the potential of alpha-HLA-G-EV as a versatile platform for precise and efficient cancer treatment.
Nat+Commun 2025 ; ? (?): ?
