Abstract

Exosomes are a novel and promising drug delivery platform because of their endogenous origin, stability, biocompatibility, and other unique features. As the efficient loading and delivery of long RNA to target cells for therapeutic purposes remains challenging, a new exosome-based RNA delivery system is proposed using a controllable RNA enrichment and releasing protocol. The system employs RNA aptamer–protein interactions and reversible light-inducible protein–protein interaction modules by remolding exosome producer cells. Endogenous microRNA 21 (miR-21) sponges, inhibitors of miR-21, are successfully enriched on the plasma membrane and are sorted into exosomes by the biogenesis of the exosomes. The loading capacity of miR-21 sponges is enhanced by 14-fold in the light-inducible loading system. In addition, targeted delivery of miR-21 to leukemia cells is achieved by modifying exosomes with the cholesterol-conjugated aptamer AS1411, resulting in significant cell apoptosis by blocking the function of miR-21 in leukemia cells. This work provides an exosome-based light-inducible vehicle to efficiently load and deliver long endogenous RNA, which can enable more RNA-based therapeutics for personalized cancer medicine.