Tumor derived small extracellular vesicles (TsEVs) display a great potential as efficient nanocarriers for
chemotherapy because of their intrinsic targeting ability. However, the inherited risks of their original cargos (like loaded
proteins or RNAs) from parent
cancer cells in
tumor progression severely hinder the practical application. In this study, a
saponin-mediated cargo elimination strategy was established and practiced in
glioblastoma (GBM) cell-derived small extracellular vesicles (GBM-sEVs). A high eliminating efficacy of the cargo molecules was confirmed by systematic analysis of the original
proteins and RNAs in GBM-sEVs. In addition, the inherited functions of GBM-sEVs to promote GBM progression vanished after
saponin treatment. Moreover, the results of cellular uptake analysis and in vivo imaging analysis demonstrated that
saponin treatment preserved the homotypic targeting ability of GBM-sEVs. Thus, we developed an efficient nanocarrier with improved biosafety for GBM suppression. Furthermore,
doxorubicin (DOX) transported by the
saponin-treated GBM-sEVs (sa-GBM-sEVs) displayed an effective
tumor suppression in both subcutaneous and orthotopic GBM models of mouse. Collectively, this study provides a feasible way to avoid the potential protumoral risks of TsEVs and can advance the clinical application of TsEVs in
chemotherapy.