Functionalizing plasma-extracellular for targeted drug delivery strategies

Extracellular vesicles (EVs) have emerged as potential vehicles for targeted drug delivery and diagnostic applications. However, achieving consistent and reliable functionalization of EV membranes remains a challenge. Copper-catalyzed click chemistry, commonly used for EV surface modification, poses limitations due to cytotoxicity and interference with biological systems. To overcome these limitations, researchers at the University of Genova have developed a standardized method for functionalizing an EV membrane via copper-free click chemistry. EVs derived from plasma hold immense potential as diagnostic and therapeutic agents. However, the isolation and functionalization of EVs from such a complex biofluid represent considerable challenges. The researchers compared three different EV isolation methods to obtain an EV suspension with an optimal purity/yield ratio, and they identified sucrose cushion ultracentrifugation (sUC) as the ideal protocol. They then optimized the reaction conditions to successfully functionalize the plasma-EV surface through a copper-free click chemistry strategy with a fluorescently labeled azide, used as a proof-of-principle molecule. Click-EVs maintained their identity, size, and, more importantly, capacity to be efficiently taken up by responder tumor cells. Moreover, once internalized, click EVs partially followed the endosomal recycling route. The optimized reaction conditions and characterization techniques presented in this study offer a foundation for future investigations and applications of functionalized EVs in drug delivery, diagnostics, and therapeutics.

Ciferri MC, Bruno S, Rosenwasser N, Gorgun C, Reverberi D, Gagliani MC, Cortese K, Grange C, Bussolati B, Quarto R, Tasso R. (2024) Standardized Method to Functionalize Plasma-Extracellular Vesicles via Copper-Free Click Chemistry for Targeted Drug Delivery Strategies. ACS Appl Bio Mater [Epub ahead of print]. [abstract]

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