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 wit... More
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.
