Exosomes as Anticancer Drug Delivery Vehicles: Prospects and Challenges

Abstract

Exosomes, a subset of extracellular vesicles, are widely present in various body fluids and are involved in mediating intercellular communication. They have received extensive attention as diagnostic markers. The excellent physicochemical and biological properties of exosomes make them great potential drug delivery vehicles for the treatment of cancer and other diseases. However, various challenges need to be addressed for the clinical application of exosomes. This review introduces the biogenesis and uptake of exosomes and compares different approaches for isolation and drug loading, focusing on the application and current challenges of exosomes as drug delivery vehicles in cancer therapy.

Endogenous Lipid Carriers—Bench-to-Bedside Roadblocks in Production and Drug Loading of Exosomes

“…Although exosomes have been shown to possess invaluable qualities for use in nanomedicine, their low production rate in unaltered cell cultures remains a key challenge, preventing bench-to-bedside use. In addition to the low production of exosomes, large variability in their size also exists, resulting in a lack of reproducibility in batches [ 1 , 7 , 8 ]. Consequently, the need remains to develop techniques that increase exosome production, maintain constant morphology, and limit any negative impact on cell cultures.…”

“…Exosomes have shown favorable biocompatibility and therapeutic targeting abilities, thus making them valuable as a potential drug delivery tool. However, several factors, such as the exosome size, the pharmacokinetics of the drug, and the drug size, may hinder the efficiency of drug loading and require more specialized techniques [ 6 , 8 , 29 , 30 ]. For example, an exosome of a larger size may be loaded with a drug more easily than one with a smaller size.…”

“…However, the use of saponins may also affect biomolecules, and thus, requires purification before clinical use. Mechanical methods, such as sonication, nanoporation, and electroporation have been shown to successfully load small molecules and macromolecules into exosomes [ 8 , 30 , 47 , 48 ]. Research conducted by C Liu et al, for example, incorporated one of the mechanical techniques, i.e., microfluidic sonication, to effectively load PLGA into exosomes isolated from a human lung carcinoma cell line (A549) [ 33 ].…”

Exosomes for angiogenesis induction in ischemic disorders

“…Exosome can also serve as an ideal vehicle for drug delivery. Various drugs as chemotherapeutics and angiogenesis‐stimulators could be loaded on exosomes and delivered different biomedical components to target tissues with great efficacy 168 . As naked exosomes undergo extensive phagocytosis and clearance shortly after transplantation, it has been shown that embedding exosomes on biomaterials such as stents, cardiac patches and cell sheets could profoundly enhance their sustainability and therapeutic efficacy 169 …”

“…Various drugs as chemotherapeutics and angiogenesis-stimulators could be loaded on exosomes and delivered different biomedical components to target tissues with great efficacy. 168 As naked exosomes undergo extensive phagocytosis and clearance shortly after transplantation, it has been shown that embedding exosomes on biomaterials such as stents, cardiac patches and cell sheets could profoundly enhance their sustainability and therapeutic efficacy. 169 Tumour-associated exosomes contain considerable angiogenic molecules since angiogenesis is a crucial necessity for tumour development, expansion and far metastasis.…”