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Review
. 2021 Aug 28:10:281-294.
doi: 10.1016/j.bioactmat.2021.08.029. eCollection 2022 Apr.

Exosomes: Small vesicles with big roles in cancer, vaccine development, and therapeutics

Abhimanyu Thakur  1   2 , Diana Carolina Parra  3 , Pedram Motallebnejad  1   2 , Marcelo Brocchi  3 , Huanhuan Joyce Chen  1   2
Affiliations
Review

Exosomes: Small vesicles with big roles in cancer, vaccine development, and therapeutics

Abhimanyu Thakur et al. Bioact Mater. .

Abstract

Cancer is a deadly disease that is globally and consistently one of the leading causes of mortality every year. Despite the availability of chemotherapy, radiotherapy, immunotherapy, and surgery, a cure for cancer has not been attained. Recently, exosomes have gained significant attention due to the therapeutic potential of their various components including proteins, lipids, nucleic acids, miRNAs, and lncRNAs. Exosomes constitute a set of tiny extracellular vesicles with an approximate diameter of 30-100 nm. They are released from different cells and are present in biofluids including blood, cerebrospinal fluid (CSF), and urine. They perform crucial multifaceted functions in the malignant progression of cancer via autocrine, paracrine, and endocrine communications. The ability of exosomes to carry different cargoes including drug and molecular information to recipient cells make them a novel tool for cancer therapeutics. In this review, we discuss the major components of exosomes and their role in cancer progression. We also review important literature about the potential role of exosomes as vaccines and delivery carriers in the context of cancer therapeutics.

Keywords: Cancer; Exosomal delivery system; Exosomal vaccine; Exosome; Extracellular vesicles; Therapeutics.

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Conflict of interest statement

None.

Figures

Image 1
Graphical abstract
Fig. 1
Fig. 1
Modulation of various events in the TME via exosomal communication. Cancer cell-derived exosomes communicate with both autologous cancer cells and heterologous stromal cells, and participate in different biological phenomena including immunosuppression, cancer metastasis, angiogenesis, migration, and proliferation by altering the metabolic status of recipient cells including enhanced glycolysis. Exosomes released from drug-resistant cancer cells are internalized by drug-sensitive cancer cells resulting in augmented glycolysis, causing development of drug resistance in the recipient cells. Further, cancer cell-derived exosomes cause changes in the surrounding microenvironment including development of an acidic extracellular environment, or preparation of pre-metastatic niche, leading to cancer metastasis. Cancer cell-derived exosomes also activate the differentiation of fibroblasts into CAFs.
Fig. 2
Fig. 2
Schematic representation of the major components of a typical exosome. An exosome is composed of a lipid bilayer membranous structure that comprises various functional constituents including protein, lipid, miRNA, lncRNA, and other components such as nucleic acids, signaling molecule, and transporters. The exosomal components play a crucial role in cancer progression and act as potential biomarkers. Moreover, they can be employed for therapeutic purposes.
Fig. 3
Fig. 3
Potential application of exosomes in immunotherapy and cancer vaccines. Schematic representation showing the cascade of events followed by release of exosomes from B cells, DCs, macrophages, cancer cells, and normal cells, that can be employed in strategies for exosome-based cancer immunotherapy.
Fig. 4
Fig. 4
Various methods of loading cargoes in exosomes for therapeutic delivery. In pre-loading methods, therapeutic molecules are incorporated into donor cells before the production of exosomes. During exosome biogenesis, incorporated molecules are packaged within exosomes to be used for therapeutic purposes. miRNA, siRNA, and mRNA can be loaded into parent cells through transfection (A). Moreover, some parent cells can uptake drug molecules by passive diffusion when they are co-incubated (B). Engineered exosomes can be produced through introduction of plasmids into parent cells to induce the expression of therapeutic molecules in exosomes (C). In post-loading methods, drug molecules are loaded directly into exosomes after isolation through physical and chemical methods. Physical methods such as electroporation (D), sonication (E), simple incubation (F), extrusion (G), and freeze/thaw cycles (H) increase exosome membrane permeability to uptake drug molecules. Chemical methods such as saponin treatment (I) and click chemistry (J) can also be used. Saponin treatment promotes the formation of pores due to its interaction with membrane cholesterol, while click chemistry enables the binding of drug molecules to the external surface of the exosome membrane. Created withBioRender.com.
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