Cytochalasin D-induced cytoskeletal remodeling with MYH9 enhances release of extracellular vesicles for therapeutic application.

Authors

Woocheol Jung, Sang Soo Kim, Shinwon Chae, Bok Sil Hong, Eun-Young Lee, Daehee Hwang, Yong Song Gho, Dongsic Choi

Published in

Biomaterials. Volume 338. Issue Pt B. Pages 124716. Oct 19, 2026. Epub Oct 19, 2026.

Abstract

Extracellular vesicles (EVs) hold great potential as therapeutic vehicles, but their clinical application is limited by low production yields. Here, we explored whether the pharmacological disruption of the actin cytoskeleton using cytochalasin D (CytoD) could enhance EV release while maintaining properties essential for therapeutic use. We examined monocytic U937 cells and colorectal cancer SW480 cells, discovering that CytoD increased EV production by approximately 8.27-fold in U937 cells and 10.06-fold in SW480 cells, while largely preserving the size distribution and surface charge of the EVs. Density gradient ultracentrifugation and label-free quantitative proteomics revealed that CytoD not only increased overall EV release but also selectively remodeled EV proteins. Notably, CytoD-EVs retained lineage-associated membrane proteins such as LFA-1 and showed an enrichment of cytoskeleton-related regulators, particularly MYH9, as well as proteins involved in adhesion and membrane trafficking. We observed the recruitment of MYH9 to membrane blebs,and both pharmacological inhibition with blebbistatin and MYH9 knockdown suppressed EV release, indicating that actomyosin-dependent contractility stimulates EV shedding. Importantly, CytoD-EVs proved to be highly effective drug carriers that doxorubicin-loaded EVs efficiently delivered cargo to recipient cells and induced greater cytotoxicity than free doxorubicin at equivalent doses. Overall, these findings demonstrate that CytoD-induced cytoskeletal remodeling enhances EV production through MYH9-associated membrane dynamics while preserving their capacity for therapeutic delivery. Thus, our findings establish CytoD-induced EV biogenesis as a robust, scalable, and translationally applicable platform for advanced EV-based drug delivery systems.

PMID:
42927683
Bibliographic data and abstract were imported from PubMed on 26 Oct 2026.

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