Extracellular Vesicles As Drug Targets and Delivery Vehicles for Cancer Therapy

Overview

Journal Pharmaceutics

Publisher MDPI

Date 2022 Dec 23

PMID 36559315

Authors

Sai V Chitti

Christina Nedeva

Raja Manickam

Pamali Fonseka

Suresh Mathivanan

Affiliations

Soon will be listed here.

Abstract

Extracellular vesicles (EVs) are particles that are released from cells into the extracellular space both under pathological and normal conditions. It is now well established that cancer cells secrete more EVs compared to non-cancerous cells and that, captivatingly, several proteins that are involved in EV biogenesis and secretion are upregulated in various tumours. Recent studies have revealed that EVs facilitate the interaction between cancer cells and their microenvironment and play a substantial role in the growth of tumours. As EVs are involved in several aspects of cancer progression including angiogenesis, organotropism, pre-metastatic niche formation, fostering of metastasis, and chemoresistance, inhibiting the release of EVs from cancer and the surrounding tumour microenvironment cells has been proposed as an ideal strategy to treat cancer and associated paraneoplastic syndromes. Lately, EVs have shown immense benefits in preclinical settings as a novel drug delivery vehicle. This review provides a brief overview of the role of EVs in various hallmarks of cancer, focusing on (i) strategies to treat cancer by therapeutically targeting the release of tumour-derived EVs and (ii) EVs as valuable drug delivery vehicles. Furthermore, we also outline the drawbacks of the existing anti-cancer treatments and the future prospective of EV-based therapeutics.

Citing Articles

G protein-coupled receptors: a gateway to targeting oncogenic EVs?.

Di Niro L, Linders A, Glynn T, Pegtel D, Siderius M, Crudden C Extracell Vesicles Circ Nucl Acids. 2024; 5(2):233-248.

PMID: 39698539 PMC: 11648488. DOI: 10.20517/evcna.2024.10.

Unlocking the Secrets of Extracellular Vesicles: Orchestrating Tumor Microenvironment Dynamics in Metastasis, Drug Resistance, and Immune Evasion.

Mir R, Baba S, Elfaki I, Algehainy N, Alanazi M, Altemani F J Cancer. 2024; 15(19):6383-6415.

PMID: 39513123 PMC: 11540496. DOI: 10.7150/jca.98426.

Chemoresistance and the tumor microenvironment: the critical role of cell-cell communication.

Wilczynski B, Dabrowska A, Kulbacka J, Baczynska D Cell Commun Signal. 2024; 22(1):486.

PMID: 39390572 PMC: 11468187. DOI: 10.1186/s12964-024-01857-7.

Extracellular Vesicles as Drug Delivery System for Cancer Therapy.

Wang J, Yin B, Lian J, Wang X Pharmaceutics. 2024; 16(8).

PMID: 39204374 PMC: 11359799. DOI: 10.3390/pharmaceutics16081029.

Extracellular vesicles (EVs)' journey in recipient cells: from recognition to cargo release.

Xiang H, Bao C, Chen Q, Gao Q, Wang N, Gao Q J Zhejiang Univ Sci B. 2024; 25(8):633-655.

PMID: 39155778 PMC: 11337091. DOI: 10.1631/jzus.B2300566.

References

Yang Y, Chen Y, Zhang F, Zhao Q, Zhong H . Increased anti-tumour activity by exosomes derived from doxorubicin-treated tumour cells via heat stress. Int J Hyperthermia. 2015; 31(5):498-506. DOI: 10.3109/02656736.2015.1036384. View

Shahi S, Cianciarulo C, Nedeva C, Mathivanan S . Extracellular Vesicles Regulate Cancer Metastasis. Subcell Biochem. 2021; 97:275-296. DOI: 10.1007/978-3-030-67171-6_11. View

Skog J, Wurdinger T, van Rijn S, Meijer D, Gainche L, Sena-Esteves M . Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol. 2008; 10(12):1470-6. PMC: 3423894. DOI: 10.1038/ncb1800. View

Thakur A, Sidu R, Zou H, Alam M, Yang M, Lee Y . Inhibition of Glioma Cells' Proliferation by Doxorubicin-Loaded Exosomes via Microfluidics. Int J Nanomedicine. 2020; 15:8331-8343. PMC: 7605152. DOI: 10.2147/IJN.S263956. View

Cabeza L, Perazzoli G, Pena M, Cepero A, Luque C, Melguizo C . Cancer therapy based on extracellular vesicles as drug delivery vehicles. J Control Release. 2020; 327:296-315. DOI: 10.1016/j.jconrel.2020.08.018. View

Fonseka P, Chitti S, Sanwlani R, Mathivanan S . Sulfisoxazole does not inhibit the secretion of small extracellular vesicles. Nat Commun. 2021; 12(1):977. PMC: 7881022. DOI: 10.1038/s41467-021-21074-x. View

Aqil F, Munagala R, Jeyabalan J, Agrawal A, Gupta R . Exosomes for the Enhanced Tissue Bioavailability and Efficacy of Curcumin. AAPS J. 2017; 19(6):1691-1702. DOI: 10.1208/s12248-017-0154-9. View

Pathan M, Fonseka P, Chitti S, Kang T, Sanwlani R, Van Deun J . Vesiclepedia 2019: a compendium of RNA, proteins, lipids and metabolites in extracellular vesicles. Nucleic Acids Res. 2018; 47(D1):D516-D519. PMC: 6323905. DOI: 10.1093/nar/gky1029. View

Xie X, Nie H, Zhou Y, Lian S, Mei H, Lu Y . Eliminating blood oncogenic exosomes into the small intestine with aptamer-functionalized nanoparticles. Nat Commun. 2019; 10(1):5476. PMC: 6889386. DOI: 10.1038/s41467-019-13316-w. View

10.

Kosgodage U, Trindade R, Thompson P, Inal J, Lange S . Chloramidine/Bisindolylmaleimide-I-Mediated Inhibition of Exosome and Microvesicle Release and Enhanced Efficacy of Cancer Chemotherapy. Int J Mol Sci. 2017; 18(5). PMC: 5454920. DOI: 10.3390/ijms18051007. View

11.

Kandimalla R, Aqil F, Tyagi N, Gupta R . Milk exosomes: A biogenic nanocarrier for small molecules and macromolecules to combat cancer. Am J Reprod Immunol. 2020; 85(2):e13349. DOI: 10.1111/aji.13349. View

12.

Bobrie A, Krumeich S, Reyal F, Recchi C, Moita L, Seabra M . Rab27a supports exosome-dependent and -independent mechanisms that modify the tumor microenvironment and can promote tumor progression. Cancer Res. 2012; 72(19):4920-30. DOI: 10.1158/0008-5472.CAN-12-0925. View

13.

Borghesan M, Fafian-Labora J, Eleftheriadou O, Carpintero-Fernandez P, Paez-Ribes M, Vizcay-Barrena G . Small Extracellular Vesicles Are Key Regulators of Non-cell Autonomous Intercellular Communication in Senescence via the Interferon Protein IFITM3. Cell Rep. 2019; 27(13):3956-3971.e6. PMC: 6613042. DOI: 10.1016/j.celrep.2019.05.095. View

14.

Moller A, Lobb R . The evolving translational potential of small extracellular vesicles in cancer. Nat Rev Cancer. 2020; 20(12):697-709. DOI: 10.1038/s41568-020-00299-w. View

15.

Coppe J, Desprez P, Krtolica A, Campisi J . The senescence-associated secretory phenotype: the dark side of tumor suppression. Annu Rev Pathol. 2010; 5:99-118. PMC: 4166495. DOI: 10.1146/annurev-pathol-121808-102144. View

16.

Ostrowski M, Carmo N, Krumeich S, Fanget I, Raposo G, Savina A . Rab27a and Rab27b control different steps of the exosome secretion pathway. Nat Cell Biol. 2009; 12(1):19-30. DOI: 10.1038/ncb2000. View

17.

Bangham A, Standish M, Watkins J . Diffusion of univalent ions across the lamellae of swollen phospholipids. J Mol Biol. 1965; 13(1):238-52. DOI: 10.1016/s0022-2836(65)80093-6. View

18.

Pelissier Vatter F, Cioffi M, Hanna S, Castarede I, Caielli S, Pascual V . Extracellular vesicle- and particle-mediated communication shapes innate and adaptive immune responses. J Exp Med. 2021; 218(8). PMC: 8241538. DOI: 10.1084/jem.20202579. View

19.

He W, Calore F, Londhe P, Canella A, Guttridge D, Croce C . Microvesicles containing miRNAs promote muscle cell death in cancer cachexia via TLR7. Proc Natl Acad Sci U S A. 2014; 111(12):4525-9. PMC: 3970508. DOI: 10.1073/pnas.1402714111. View

20.

Fearon K, Strasser F, Anker S, Bosaeus I, Bruera E, Fainsinger R . Definition and classification of cancer cachexia: an international consensus. Lancet Oncol. 2011; 12(5):489-95. DOI: 10.1016/S1470-2045(10)70218-7. View