Reversible Charge-Mediated Capture and Release of Extracellular Vesicles Using Giant Unilamellar Vesicles
Marinella Pinelli, Gabriele Schiavi, Dalia Tarantino, Luca Valer, Martina Cortese, Michela Notarangelo, Miriam Romano, Annalisa Radeghieri, Lucia Paolini, Paolo Bergese, Vito G. D’Agostino, Martin M. Hanczyc, Silvia HollerAbstract
Extracellular vesicles (EVs) play crucial roles in intercellular communication and represent promising therapeutic vehicles, yet current isolation and manipulation methods often irreversibly alter their properties. This study presents a charge-mediated approach for the reversible interaction and release of EVs using Giant Unilamellar Vesicles (GUVs) exploiting tailored surface charges. Negatively charged EVs can be selectively bound through electrostatic interactions with positively charged GUVs, forming stable aggregates. Critically, these interactions are reversible upon the introduction of a negatively charged moiety, oleic acid, which disaggregates the complexes and releases the vesicles. Selective fusion events between oppositely charged GUVs allow modulation of internal composition, while GUVs–EVs interactions remain nonfusogenic. This reversible, charge-based platform offers advantages over current EVs’ capture methods, including simplicity, low cost, and the potential for a separation method without permanent labeling.