1 research outputs found
Extracellular vesicleâmediated protein delivery to the liver
Abstract Extracellular vesicles (EVs) are nanoscale particles that facilitate intercellular communication. They are regarded as a promising natural drug delivery system for transporting and delivering bioactive macromolecules to target cells. Recently, researchers have engineered EVs with FKBP12/FRB heterodimerization domains that interact with rapamycin to load and deliver exogenous proteins for both in vitro and in vivo applications. In this study, we examined the tissue distribution of EVs using nearâinfrared fluorescent imaging. We evaluated the effectiveness of EVâmediated delivery of Cre recombinase specifically to hepatocytes in the livers of Ai9 CreâloxP reporter mice. Intravenous injection resulted in more efficient Cre protein delivery to the liver than intraperitoneal injections. Depleting liverâresident macrophages with clodronateâencapsulated liposome preâtreatment did not enhance EVâmediated Cre delivery to hepatocytes. Moreover, we demonstrated that multiple intravenous injections of CreâEVs facilitated functional Cre delivery to hepatocytes. To the best of our knowledge, this is the first study to simultaneously investigate the tissue distribution of FKBP12/FRBâengineered EVs and their subsequent intracellular protein delivery in Ai9 CreâloxP reporter mice. These insights can inform preclinical research and contribute to developing nextâgeneration EVâbased platforms for delivering therapeutic proteins or genome editing technologies targeting the liver