Harnessing exosomes for targeted therapy: strategy and application

doi:10.12336/biomatertransl.2024.01.005

Biomaterials Translational ›› 2024, Vol. 5 ›› Issue (1): 46-58.doi: 10.12336/biomatertransl.2024.01.005

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Harnessing exosomes for targeted therapy: strategy and application

Xiaoxiang Ren¹^,⁵, Ruixue Xu²^,^*(), Chenjie Xu³^,^*(), Jiacan Su¹^,⁴^,⁵^,^*()

1 Organoid Research Center, Institute of Translational Medicine, Shanghai University, Shanghai, China
2 Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT, USA
3 Department of Biomedical Engineering, City University of Hong Kong, Hong Kong Special Administrative Region, China
4 Department of Orthopedic, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
5 National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai, China

Received:2024-01-03 Revised:2024-01-22 Accepted:2024-02-06 Online:2024-03-28 Published:2024-03-28
Contact: Ruixue Xu, ruixue.xu@yale.edu; Chenjie Xu, chenjie.xu@cityu.edu.hk; Jiacan Su, drsujiacan@163.com.

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Abstract

Abstract:

Exosomes, nanoscopic extracellular vesicles produced by cells, are pivotal in mediating intracellular communication by transporting nucleic acids, proteins, lipids, and other bioactive molecules, thereby influencing physiological and pathological states. Their endogenous origin and inherent diversity confer distinct advantages over synthetic vehicles like liposomes and nanoparticles in diagnostic and therapeutic applications. Despite their potential, the clinical utility of exosomes is hampered by challenges such as limited storage stability, yield, purity, and targeting efficiency. This review focuses on exosomes as targeted therapeutic agents, examining their biogenesis, classification, isolation, and characterisation, while also addressing the current limitations in yield, purity, and targeting. We delve into the literature to propose optimisation strategies that can enhance their therapeutic efficacy and accelerate the translation of exosome-based therapies into clinical practice.

Key words: biomedical engineering, exosomes, modification, nanotechnology, targeted therapy

Cite this article

Figures/Tables 7

Figure 1. Engineered exosomes offer a targeted therapeutic approach, enhanced by direct or indirect modifications to treat diseases with precision and reduced toxicity. Created with Adobe Photoshop 2024.

Figure 2. The content and production of exosomes. ILV: intraluminal vesicle; MVB: multivesicular body; PM: plasma membrane. Created with BioRender.com.

Figure 3. The process of targeted therapy of exosomes. 1. Cells culture: The process begins with the culture of cells, which are the source of exosomes. 2. Exosome production and purification: Following cell culture, exosomes are produced and then isolated and purified from the cell media. 3. Cargo-loading exosomes: The isolated exosomes are then loaded with therapeutic cargo. This step involves incorporating the desired molecules, such as drugs or proteins, into the exosomes. 4. Exosome quality control and administration: After loading the cargo, the exosomes undergo quality control to ensure they meet the necessary standards for therapeutic use. Once approved, they are ready for administration to the patient. 5. Targeted therapy: The final step is the administration of these engineered exosomes to the patient, where they can deliver their therapeutic cargo to the targeted tissues or cells in the body. This sequence represents the full cycle from cell culture to the delivery of targeted therapy using exosomes. Created with BioRender.com.

Figure 4. The modification strategy of exosomes. DSPE: 1,2-distearoyl-sn-glycero-3-phosphoethanolamine; Lamp2b: lysosome-associated membrane protein 2b. Created with BioRender.com.

Figure 5. Genetically modified exosomes. (A) Exosomes modified with RVG-Lamp2b promote neurogenesis. Reprinted from Yang et al.39 (B) T7-peptide decorated exosomes deliver microRNA-21 antisense oligonucleotides to the brain. Reprinted from Kim et al.41 Copyright 2019, with permission from Elsevier B.V. (C) Binding of iRGD-Exos to a human breast cancer cell line in vitro. Reprinted from Tian et al.43 Copyright 2013, with permission from Elsevier B.V. (D) CD9-HuR functionalized exosomes encapsulated with miRNA or CRISPR/dCas9. Reprinted with permission from Li et al.45 Copyright 2019, American Chemical Society. Alix: apoptosis linked gene-2-interacting protein X; BM-MSC: bone marrow derived mesenchymal stem cell; CMV: cytomegalovirus; DiO: 3,3′-dioctadecyloxacarbocyanine perchlorate; DiR: 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindotricarbocyanine iodide; Exos: exosomes; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GM130: Golgi matrix protein 130; HuR: human antigen R; miRNA: microRNA; RVG: rabies virus glycoprotein.

Figure 6. Direct modified exosomes. (A) Screening for exosomal anchor peptides on exosomes. Reprinted from Gao et al.50 Copyright 2018 Gao et al., some rights reserved; exclusive licensee American Association for the Advancement of Science. (B) Cholesterol-oligonucleotide tethering method on exosome membrane. Reprinted with permission from Yerneni et al.51 Copyright 2019, American Chemical Society. (C) Epidermal growth factor receptor (EGFR) ligands on the outer surfaces of the exosomes. Reprinted from Ohno et al.57 Copyright ? 2013 The American Society of Gene & Cell Therapy. Published by Elsevier Inc. A.U.: augmentation unit; dsRNA: double-stranded RNA; EGF: epidermal growth factor; EXO: exosome; i.v.: intravenous; Ph.D. phage library: Ph.D.-12 phage display library (New England BioLabs, Ipswich, MA, USA); PMO: phosphorodiamidate morpholino oligomer; RT: room temperature; ssRNA: single-stranded RNA.

Figure 7. The applications of targeted therapy of exosomes. Created with BioRender.com.

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Harnessing exosomes for targeted therapy: strategy and application

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