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Progress in Chemistry 2022, Vol. 34 Issue (4): 773-786 DOI: 10.7536/PC210901   Next Articles

• Review •

Exosomes Drug Delivery Systems and Their Application in Tumor Treatment

Xiaofeng Chen, Kaiyuan Wang, Fangming Liang, Ruiqi Jiang, Jin Sun()   

  1. Wuya College of Innovation, Shenyang Pharmaceutical University,Shenyang 110016, China
  • Received: Revised: Online: Published:
  • Contact: Jin Sun
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Cancer is the second leading cause of death in the world, and the incidence rate of cancer remains high every year. Although existing treatments have made significant progress in the past decade, due to the non-specific cytotoxicity, poor biocompatibility and low bioavailability of existing anti-tumor drugs, the therapeutic effect of chemotherapy and other methods is poor. Exosomes are membrane vesicles secreted by various kinds of cells with phospholipid bilayer structure and nano particle size (30~100 nm). Exosomes are the media of information exchange and material transportation between cells, carrying proteins, lipids, nucleic acids and other substances of host cells. With the in-depth study of exosomes, their application is more and more widespread. In the process of intercellular communication, exosomes can regulate the biological response of target cells, which may promote or inhibit disease. They have good biocompatibility, high stability and excellent targetability. Exosomes serving as potentially effective drug delivery systems in cancer treatment have attracted increasing attention. In order to enhance the therapeutic effect of exosomes and reduce the toxicity of drugs to normal cells, it is necessary to improve the targetability of exosomes. Researchers try to customize exosomes with different targeting categories and abilities by modifying exosomes in various ways, which endows exosomes with broad prospects in the field of targeted therapy of tumors. This review highlights the design strategy of exosomes as drug carriers to target tumors, and tries to provide new insights of exosomes-based nanocarriers in various tumor treatment. Besides, this review mainly introduces the biogenesis of exosomes, the physiological function of exosomes and their separation methods. Particular attention is paid to the design strategy of engineered exosomes targeting tumors, including using exosomes from different sources, different surface modification methods and different stimuli-responsive exosomes. Finally, we summarize and discuss the progress of exosomes as drug carriers to solid tumors, and the deficiencies of exosomes in clinical application.

Contents

1 Introduction

2 Exosomes and their characteristics

2.1 Composition of exosomes

2.2 Biogenesis of exosomes

2.3 Physiological function of exosomes

2.4 Isolation of exosomes

2.5 Drug loading mechanism of exosomes

3 The design strategy of engineered exosomes targeting tumors

3.1 Exosomes from different cell sources

3.2 Surface modification of exosomes

3.3 Stimuli-responsive exosomes

4 Application of exosomes as drug delivery carriers in tumor therapy

4.1 Lung cancer

4.2 Pancreatic cancer

4.3 Breast cancer

4.4 Colorectal cancer

4.5 Glioblastoma

5 Conclusion and outlook

Key words: exosome, drug carrier, tumor therapy, delivery system
Fig. 1 Biogenesis of exosomes[44]
Table 1 Comparison of advantages and disadvantages of Isolation of exosomes
Advantages Disadvantages
Ultracentrifugation Operation is simple; Low-cost. Long time required; Low recovery and purity; Demand large sample.
Immunoseparation High recovery and purity; Strong specificity; High sensitivity; Demand small sample. Long time required; High-cost.
Polymer Precipitation Operation is simple; Time saving; Suitable for processing large samples. Low recovery and purity; Low specificity; Polymer produced is difficult to remove.
Size-exclusion Chromatography Operation is simple; Time saving; High recovery and purity. High-cost.
Fig. 2 Isolation of exosomes[40]
Table 2 Comparison of advantages and disadvantages of different techniques for loading cargos in exosomes
Advantages Disadvantages
Electroporation Operation is simple; Suitable for large molecules loading. Low loading efficiency; Destroy the integrity of EVs.
Incubation Operation is simple; No need to add extra active substances. Low loading efficiency.
Sonication High loading efficiency; Sustained drug release; Suitable for small RNAs. Potential deformation of membrane of EVs; Not efficient for hydrophobic drugs.
Click Chemistry No by-products; High Selectivity; Mild reaction conditions; No destruction on the structure and function of exosomes. Copper can be easily oxidized and inactivated.
Fig. 3 Schematic illustration of E-PSiNPs as drug carriers for targeted cancer chemotherapy[56]
Fig. 4 Chemical bonding modification of exosomes[95]
Fig. 5 Schematic illustration of construction and delivery of drug-loaded SMNC-EXOs[98]
Fig. 6 (A) Schematic illustration of the design of FA-AuNR@RGD-DOX-Exos and their antitumor effect under NIR irradiation. The therapeutic efficiency of FA-AuNR@RGD-DOX-Exos was evaluated in a tumor-bearing mouse model. (B) Schematic illustration of FA-AuNR@RGD-DOX-Exos as a robust nanoplatform for targeted delivery and chemo-photothermal synergistic tumor therapy[102]
Fig. 7 Illustration of endogenous nanosonosensitizers for focused US-augmented targeting delivery to recognize homotypic cancer cell, stimuli-responsive drug release, and enhanced SDT[107]
Fig. 8 Schematic representation of the exosome-like sequential-bioactivating paclitaxel prodrug nanoplatform with CTCs clearance, CuB-mediated metastasis suppression, ROS enhancement, and cascade amplified PTX chemotherapy[1]
Fig. 9 Schematic representation of RGE-Exo-SPION/Cur synthesis[124]
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