Targeting tripel-negative breast cancer using bioengineered extracellular vesicles
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Date
2025-07-08
Authors
Gaser, Hiba
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Abstract
Triple-negative breast cancer (TNBC) is a highly aggressive and heterogeneous subtype of breast cancer with few available targeted therapies. Antibody-functionalized extracellular vesicles (EVs) represent a promising strategy for precision drug delivery due to their innate biocompatibility, nanoscale size, and ability to traverse biological barriers. In this study, EVs were derived from HEK293 cells engineered to express CD63-z-domain fusion constructs, allowing Fc-mediated attachment of antibodies. These EVs were functionalized with atezolizumab (anti–PD-L1), sacituzumab (anti–Trop-2), or isotype control IgG, and loaded with the chemotherapeutic agent epirubicin via electroporation. Flow cytometry revealed enhanced, dose-dependent uptake of antibody-decorated EVs in MDA-MB-231 cells, with atezolizumab showing superior targeting efficiency. Epirubicin-loaded EVs significantly reduced cell viability compared to free epirubicin, particularly at sub-therapeutic concentrations, and demonstrated broader cytotoxic activity in T47D cells. These findings support the use of this modular EV platform for tunable targeting and effective drug delivery in TNBC and potentially other malignancies, positioning antibody-functionalized EVs as a compelling avenue for next-generation nanotherapeutics.
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Keywords
Extracellular vesicles, Triple-negative breast cancer, Antibodyfunctionalization, Epirubicin loading, Nanotherapeutics