title: Biodistribution and delivery efficiency of unmodified tumor-derived exosomes.
abstract: The use of exosomes as a drug delivery vehicle has gained considerable interest. To establish if exosomes could be utilized effectively for drug delivery, a better understanding of their in vivo fate must be established. Through comparisons to liposomal formulations, which have been studied extensively for the last thirty years, we were able to make some comprehensive conclusions about the fate of unmodified tumor-derived exosomes in vivo. We observed a comparable rapid clearance and minimal tumor accumulation of intravenously-injected exosomes, PC:Chol liposomes, and liposomes formulated with the lipid extract of exosomes, suggesting that the unique protein and lipid composition of exosomes does not appreciably impact exosomes' rate of clearance and biodistribution. This rapid clearance along with minimal tumor accumulation of unmodified exosomes limits their use as an anti-cancer drug delivery vehicle; however, when delivered intratumorally, exosomes remained associated with tumor tissue to a significantly greater extent than PC:Chol liposomes. Furthermore, experiments utilizing mice with impaired adaptive or innate immune systems, revealed the significance of the innate immune system along with the complement protein C5 on exosomes' rate of clearance.
authors.affiliation: University of Colorado Denver, Anschutz Medical Campus, Department of Pharmaceutical Sciences, Aurora, CO, USA.
authors.forename: Tyson
authors.initials: T
authors.lastname: Smyth
authors.affiliation: University of Colorado Denver, Anschutz Medical Campus, Department of Pharmaceutical Sciences, Aurora, CO, USA.
authors.forename: Max
authors.initials: M
authors.lastname: Kullberg
authors.affiliation: Ulm University Hospital, Clinic for Nuclear Medicine, Ulm, Germany.
authors.forename: Noeen
authors.initials: N
authors.lastname: Malik
authors.affiliation: Stony Brook School of Medicine, Department of Psychiatry, Stony Brook, NY, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Smith-Jones
authors.affiliation: University of Colorado Denver, Anschutz Medical Campus, Department of Neurosurgery, Aurora, CO, USA.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Graner
authors.affiliation: University of Colorado Denver, Anschutz Medical Campus, Department of Pharmaceutical Sciences, Aurora, CO, USA. Electronic address: Tom.Anchordoquy@ucdenver.edu.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Anchordoquy
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D002460:Cell Line; D002626:Chemistry, Pharmaceutical; D002794:Choline; D004317:Doxorubicin / Q000008:administration & dosage / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D055354:Exosomes / Q000737:chemistry / Q000378:metabolism*; D007275:Injections, Intravenous; D008081:Liposomes / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000737:chemistry*; D010316:Particle Size; D014677:Pharmaceutical Vehicles; D010713:Phosphatidylcholines; D014018:Tissue Distribution
chemical_list: D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D008081:Liposomes; D014677:Pharmaceutical Vehicles; D010713:Phosphatidylcholines; D004317:Doxorubicin; D002794:Choline
keywords: Biodistribution; Exosomes; Intratumoral injection; Intravenous injection; Liposomes