Tunable plasma coating method modulates surface charge and protein corona of cell-derived nanovesicles for improved systemic drug delivery

<h2>Summary</h2> Cell-derived nanovesicles are emerging as versatile carriers for therapeutic delivery, but their surface charge and protein corona critically influence their biological behavior. Here, plasma coating is introduced as a rapid, tunable, and reagent-free strategy to transiently modify vesicle surface properties. Plasma exposure reverses the membrane charge of cell membrane-derived nanovesicles in a treatment time-dependent and reversible manner. Moreover, plasma treatment modulates the density and composition of the protein corona, yielding a profile associated with reduced immune recognition and enhanced cellular interaction. These changes collectively improve cellular uptake, drug delivery efficiency, and therapeutic activity <i>in vivo</i>. This controllable and biocompatible surface-engineering approach offers a scalable platform for optimizing nanovesicle-based drug delivery and related biomedical applications.