Extracellular Vesicles: An Emerging Nanoplatform for Cancer Therapy

Overview

Journal Front Oncol

Specialty Oncology

Date 2021 Feb 25

PMID 33628730

Citations 32

Authors

Yifan Ma

Shiyan Dong

Xuefeng Li

Betty Y S Kim

Zhaogang Yang

Wen Jiang

Affiliations

Soon will be listed here.

Abstract

Extracellular vesicles (EVs) are cell-derived membrane particles that represent an endogenous mechanism for cell-to-cell communication. Since discovering that EVs have multiple advantages over currently available delivery platforms, such as their ability to overcome natural barriers, intrinsic cell targeting properties, and circulation stability, the potential use of EVs as therapeutic nanoplatforms for cancer studies has attracted considerable interest. To fully elucidate EVs' therapeutic function for treating cancer, all current knowledge about cellular uptake and trafficking of EVs will be initially reviewed. In order to further improve EVs as anticancer therapeutics, engineering strategies for cancer therapy have been widely explored in the last decade, along with other cancer therapies. However, therapeutic applications of EVs as drug delivery systems have been limited because of immunological concerns, lack of methods to scale EV production, and efficient drug loading. We will review and discuss recent progress and remaining challenges in developing EVs as a delivery nanoplatform for cancer therapy.

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References

Zaky S, Lee K, Gao J, Jensen A, Close J, Wang Y . Poly(glycerol sebacate) elastomer: a novel material for mechanically loaded bone regeneration. Tissue Eng Part A. 2013; 20(1-2):45-53. DOI: 10.1089/ten.TEA.2013.0172. View

Kucharzewska P, Christianson H, Welch J, Svensson K, Fredlund E, Ringner M . Exosomes reflect the hypoxic status of glioma cells and mediate hypoxia-dependent activation of vascular cells during tumor development. Proc Natl Acad Sci U S A. 2013; 110(18):7312-7. PMC: 3645587. DOI: 10.1073/pnas.1220998110. View

Sun J, Jiang L, Lin Y, Gerhard E, Jiang X, Li L . Enhanced anticancer efficacy of paclitaxel through multistage tumor-targeting liposomes modified with RGD and KLA peptides. Int J Nanomedicine. 2017; 12:1517-1537. PMC: 5338999. DOI: 10.2147/IJN.S122859. View

Wang M, Altinoglu S, Takeda Y, Xu Q . Integrating Protein Engineering and Bioorthogonal Click Conjugation for Extracellular Vesicle Modulation and Intracellular Delivery. PLoS One. 2015; 10(11):e0141860. PMC: 4631329. DOI: 10.1371/journal.pone.0141860. View

El Andaloussi S, Mager I, Breakefield X, Wood M . Extracellular vesicles: biology and emerging therapeutic opportunities. Nat Rev Drug Discov. 2013; 12(5):347-57. DOI: 10.1038/nrd3978. 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

Zhang Y, Liu Y, Liu H, Tang W . Exosomes: biogenesis, biologic function and clinical potential. Cell Biosci. 2019; 9:19. PMC: 6377728. DOI: 10.1186/s13578-019-0282-2. View

de Araujo Farias V, OValle F, Serrano-Saenz S, Anderson P, Andres E, Lopez-Penalver J . Exosomes derived from mesenchymal stem cells enhance radiotherapy-induced cell death in tumor and metastatic tumor foci. Mol Cancer. 2018; 17(1):122. PMC: 6094906. DOI: 10.1186/s12943-018-0867-0. View

Munich S, Sobo-Vujanovic A, Buchser W, Beer-Stolz D, Vujanovic N . Dendritic cell exosomes directly kill tumor cells and activate natural killer cells via TNF superfamily ligands. Oncoimmunology. 2012; 1(7):1074-1083. PMC: 3494621. DOI: 10.4161/onci.20897. View

10.

Arscott W, Tandle A, Zhao S, Shabason J, Gordon I, Schlaff C . Ionizing radiation and glioblastoma exosomes: implications in tumor biology and cell migration. Transl Oncol. 2014; 6(6):638-48. PMC: 3890698. DOI: 10.1593/tlo.13640. View

11.

Maus R, Jakub J, Nevala W, Christensen T, Noble-Orcutt K, Sachs Z . Human Melanoma-Derived Extracellular Vesicles Regulate Dendritic Cell Maturation. Front Immunol. 2017; 8:358. PMC: 5372822. DOI: 10.3389/fimmu.2017.00358. View

12.

Antimisiaris S, Mourtas S, Marazioti A . Exosomes and Exosome-Inspired Vesicles for Targeted Drug Delivery. Pharmaceutics. 2018; 10(4). PMC: 6321407. DOI: 10.3390/pharmaceutics10040218. View

13.

Xiao L, Erb U, Zhao K, Hackert T, Zoller M . Efficacy of vaccination with tumor-exosome loaded dendritic cells combined with cytotoxic drug treatment in pancreatic cancer. Oncoimmunology. 2017; 6(6):e1319044. PMC: 5486185. DOI: 10.1080/2162402X.2017.1319044. View

14.

Sun J, Yang Z, Teng L . Nanotechnology and Microtechnology in Drug Delivery Systems. Dose Response. 2020; 18(2):1559325820907810. PMC: 7160771. DOI: 10.1177/1559325820907810. View

15.

Smyth T, Petrova K, Payton N, Persaud I, Redzic J, Graner M . Surface functionalization of exosomes using click chemistry. Bioconjug Chem. 2014; 25(10):1777-84. PMC: 4198107. DOI: 10.1021/bc500291r. View

16.

Mahaweni N, Kaijen-Lambers M, Dekkers J, Aerts J, Hegmans J . Tumour-derived exosomes as antigen delivery carriers in dendritic cell-based immunotherapy for malignant mesothelioma. J Extracell Vesicles. 2013; 2. PMC: 3823268. DOI: 10.3402/jev.v2i0.22492. View

17.

Samanta S, Rajasingh S, Drosos N, Zhou Z, Dawn B, Rajasingh J . Exosomes: new molecular targets of diseases. Acta Pharmacol Sin. 2017; 39(4):501-513. PMC: 5888687. DOI: 10.1038/aps.2017.162. View

18.

Cooks T, Pateras I, Jenkins L, Patel K, Robles A, Morris J . Mutant p53 cancers reprogram macrophages to tumor supporting macrophages via exosomal miR-1246. Nat Commun. 2018; 9(1):771. PMC: 5823939. DOI: 10.1038/s41467-018-03224-w. View

19.

Qi H, Liu C, Long L, Ren Y, Zhang S, Chang X . Blood Exosomes Endowed with Magnetic and Targeting Properties for Cancer Therapy. ACS Nano. 2016; 10(3):3323-33. DOI: 10.1021/acsnano.5b06939. View

20.

Fahey E, Doyle S . IL-1 Family Cytokine Regulation of Vascular Permeability and Angiogenesis. Front Immunol. 2019; 10:1426. PMC: 6603210. DOI: 10.3389/fimmu.2019.01426. View