Extracellular Vesicles: A Novel Tool in Nanomedicine and Cancer Treatment

Abstract

Extracellular vesicles are membrane-bound vesicles released by cells to mediate intercellular communication and homeostasis. Various external stimuli as well as inherent abnormalities result in alterations in the extracellular vesicle milieu. Changes to cells result in alterations in the content of the extracellular vesicle biogenesis, which may affect proximal and distal cells encountering these altered extracellular vesicles. Therefore, the examination of changes in the extracellular vesicle signature can be used to follow disease progression, reveal possible targets to improve therapy, as well as to serve as mediators of therapy. Furthermore, recent studies have developed methods to alter the cargo of extracellular vesicles to restore normal function or deliver therapeutic agents. This review will examine how extracellular vesicles from cancer cells differ from normal cells, how these altered extracellular vesicles can contribute to cancer progression, and how extracellular vesicles can be used as a therapeutic agent to target cancer cells and cancer-associated stroma. Here we present extracellular vesicles as a novel tool in nanomedicine.

Keywords: cancer; cancer treatments; cancer vaccine; drug delivery; exosomes; extracellular vesicles; gene delivery; mesenchymal stem-cell-derived extracellular vesicles; nanoparticles; protein delivery.

Figure 1

Schematic illustration depicting sources for EV collection. EVs can be isolated from various biological samples including bone marrow, cerebrospinal fluid (CSF), blood, urine, cell lysate, tissue lysate, cell culture media, and saliva and tissue biopsy.

Figure 2

Schematic illustration depicting how cancer-cell-derived EVs affect various noncancer cell populations in the TME to favor cancer progression. Cancer cells secrete EVs to affect noncancer cells that comprise the TME (shaded area). Cancer-cell-derived EVs have the ability to increase the cell growth of both endothelial cells and fibroblasts within the TME. They also induce angiogenesis by targeting the endothelial cell machinery, and they transform fibroblasts into cancer-associated fibroblasts. Cancer-cell-derived EVs also target T cells to induce immunosuppression and promote immune invasion [1].

Figure 3

Schematic illustration summarizing the use of EVs in medicine as drug delivery systems. EVs can be used in immunotherapy, such as exosomes derived from CAR-T cells, can be effective at promoting cell death via immune defense activation [63]. EVs can also be loaded with chemotherapy drugs (both hydrophobic and hydrophilic), and can safely deliver the drug to the cancer cells intact due their lipid bilayer in which the drug is enclosed. Moreover, EVs can be loaded with biomolecules such as antitumorigenic miRNAs, long noncoding RNAs, mRNAs, and proteins (e.g., tumor suppressors). Finally, EVs derived from mesenchymal stem cells can be utilized as an anticancer treatment themselves due to their ability to suppress tumor growth.