Extracellular vesicles (EVs) have been highlighted as novel drug carriers due to their unique structural properties and intrinsic features, including high stability, biocompatibility, and cell-targeting properties. Although many efforts have been made to harness these features to develop a clinically effective EV-based therapeutic system, the clinical translation of EV-based nano-drugs is hindered by their low yield and loading capacity. Herein, we present an engineering strategy that enables upscaled EV production with increased loading capacity through the secretion of EVs from cells via cytochalasin-B (CB) treatment and reduction of EV intravesicular contents through hypo-osmotic stimulation. CB (10 µg/mL) promotes cells to extrude EVs, producing ~three-fold more particles than through natural EV secretion. When CB is induced in hypotonic conditions (223 mOsm/kg), the produced EVs (hypo-CIMVs) exhibit ~68% less intravesicular protein, giving 3.4-fold enhanced drug loading capacity compared to naturally secreted EVs. By loading doxorubicin (DOX) into hypo-CIMVs, we found that hypo-CIMVs efficiently deliver their drug cargos to their target and induce up to ~1.5-fold more cell death than the free DOX. Thus, our EV engineering offers the potential for leveraging EVs as an effective drug delivery vehicle for cancer treatment.
|Publication status||Published - 2022 Jan 1|
Bibliographical noteFunding Information:
Funding: This research was funded by NSF under grant numbers DMR-1808251 and DMR-1741560 and by Milton J. Henrichs Endowed Chair fund. This research was also supported in part by the University of Wisconsin Head and Neck SPORE grant (P50-DE026787).
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
All Science Journal Classification (ASJC) codes
- Chemical Engineering(all)
- Materials Science(all)