Lab-on-a-chip system for small extracellular vesicle isolation and drug loading for small extracellular vesicle-mediated drug delivery for treatment of cancer patients

Microfluidic devices, renowned for their microscale fluid control capabilities, offer efficient extracellular vesicle (EV) purification. This study aimed to pioneer the development of a Lab-on-Chip (LOC) system for the simultaneous isolation and drug loading of EVs from serum, harnessing their innate carrier properties. The microfluidic system consists of surface acoustic wave (SAW)-based isolation and miniaturized electroporation modules. EVs sourced from human serum and MDA-MB-231 cells were isolated via both ultracentrifugation and the microfluidic system and underwent comprehensive characterization, including size and quantity assessment using zeta-sizer, transmission electron microscopy (TEM), and flow cytometry. The apoptotic activity of paclitaxel (PTX)-loaded small EV was evaluated on MCF-10A and MDA-MB-231 cells. While the binding values of CD9, CD63, and CD81 on EVs isolated through ultracentrifugation and microfluidic remained similar, significant differences emerged in their drug loading capacities. Notably, PTX-loaded EVs obtained via the microfluidic system exhibited enhanced stability and faster cellular uptake, attributed to their narrower size distribution. The microfluidic system developed in this study demonstrates its utility for efficient small EV separation, marking a significant step in the field of EV-based drug delivery.