Aptamer‐Coupled Polymer‐Grafted Fe 3 O 4 Nanoparticles for Highly Efficient Isolation of Exosomes

Abstract Exosomes, the bioactive particles secreted by various cells, are essential in mediating cellular communication. However, their small size and the interference from non‐exosome proteins present significant hurdles for their rapid and non‐destructive capture and release. To overcome these obstacles, a promising strategy to efficiently and selectively isolate exosomes from mesenchymal stem cells (MSCs) is developed by using CD63 aptamer‐conjugated magnetic nanoparticles (Fe 3 O 4 ‐Aptamer). The Fe 3 O 4 nanoparticles are first modified by RAFT polymerization of N ‐(methacryloyloxy) succinimide and oligoethylene glycol methacrylate, and subsequently, CD63 aptamers are grafted onto the surface of nanoparticles to produce Fe 3 O 4 ‐Aptamer. These aptamer units act as a “lock and key” recognition with the CD63 proteins on exosomes, enabling specific binding to exosomes. The Fe 3 O 4 ‐Aptamer can efficiently capture exosomes in a conditioned medium, and be easily collected by an external magnetic field, facilitating the facile collection and multiple‐cycle reuse of Fe 3 O 4 ‐Aptamer. By introducing the complementary sequence of the CD63 aptamer, the captured exosomes can be rapidly released from Fe 3 O 4 ‐Aptamer because of the stronger binding affinity between the complementary sequence and the aptamers. When utilized for exosome isolation, the exosome‐capture and release efficiency of Fe 3 O 4 ‐Aptamer can achieve up to ca. 82.9% and 96.1%, respectively. Thus, Fe 3 O 4 ‐Aptamer offers a promising and facile strategy for the highly efficient isolation of exosomes.