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Artificial exosomes for translational nanomedicine

Li, Yong-Jiang, Wu, Jun-Yong, Liu, Jihua, Xu, Wenjie, Qiu, Xiaohan, Huang, Si, Hu, Xiong-Bin, Xiang, Da-Xiong·2021·Journal of Nanobiotechnology
DOI 10.1186/s12951-021-00986-2PMC PMC8359033
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Abstract

Exosomes are lipid bilayer membrane vesicles and are emerging as competent nanocarriers for drug delivery. The clinical translation of exosomes faces many challenges such as massive production, standard isolation, drug loading, stability and quality control. In recent years, artificial exosomes are emerging based on nanobiotechnology to overcome the limitations of natural exosomes. Major types of artificial exosomes include ‘nanovesicles (NVs)’, ‘exosome-mimetic (EM)’ and ‘hybrid exosomes (HEs)’, which are obtained by top-down, bottom-up and biohybrid strategies, respectively. Artificial exosomes are powerful alternatives to natural exosomes for drug delivery. Here, we outline recent advances in artificial exosomes through nanobiotechnology and discuss their strengths, limitations and future perspectives. The development of artificial exosomes holds great values for translational nanomedicine.

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Fig. 1 Main strategies for obtaining artificial exosomes based on nanobiotechnology. A Top-down strategies for generating nanovesicles (NVs) by manipulating cells. Cells can be forced to pass through membrane pores or microfluidic devices to form NVs; cells can be disrupted by nitrogen cavitation to form NVs; sulfhydryl-blocking can lead to the release of small NVs from cells by cell membrane blebbing; cells exposed to alkaline solution will be broken into membrane sheets, which can form small NVs by sonication. B bottom-up strategies for generating fully artificial exosomes by supramolecular chemistry; synthetic materials (lipids) and key components (proteins) from cells can be combined to form exosome-mimetics (EMs) by supramolecular chemistry. C Biohybrid strategies for generating hybrid exosomes by fusing exosomes with liposomes. Isolated natural exosomes and synthetic liposome nanoparticles can be fused into hybrid exosomes (HEs) without affecting their intrinsic properties.
Fig. 1 Main strategies for obtaining artificial exosomes based on nanobiotechnology. A Top-down strategies for generating nanovesicles (NVs) by manipulating cells. Cells can be forced to pass through membrane pores or microfluidic devices to form NVs; cells can be disrupted by nitrogen cavitation to form NVs; sulfhydryl-blocking can lead to the release of small NVs from cells by cell membrane blebbing; cells exposed to alkaline solution will be broken into membrane sheets, which can form small NVs by sonication. B bottom-up strategies for generating fully artificial exosomes by supramolecular chemistry; synthetic materials (lipids) and key components (proteins) from cells can be combined to form exosome-mimetics (EMs) by supramolecular chemistry. C Biohybrid strategies for generating hybrid exosomes by fusing exosomes with liposomes. Isolated natural exosomes and synthetic liposome nanoparticles can be fused into hybrid exosomes (HEs) without affecting their intrinsic properties.CC BY · PubMed Central
Fig. 2 A typical top-down strategy for generating therapeutic macrophage derived-nanovesicles for tumor immunotherapy. M1 nanovesicles (M1NVs) were produced by serial extrusion of M1 macrophage induced by lipopolysaccharide (LPS). M1NV was purified by density gradient ultracentrifugation. M1NV reached the tumor site and polarized M2 tumor-associated macrophage (TAM) to anti-tumoral M1 type and induce secretion of pro-inflammatory cytokines to activate T cells. (Reprint with permission from [58]. Copyright American Chemical Society, 2018)
Fig. 2 A typical top-down strategy for generating therapeutic macrophage derived-nanovesicles for tumor immunotherapy. M1 nanovesicles (M1NVs) were produced by serial extrusion of M1 macrophage induced by lipopolysaccharide (LPS). M1NV was purified by density gradient ultracentrifugation. M1NV reached the tumor site and polarized M2 tumor-associated macrophage (TAM) to anti-tumoral M1 type and induce secretion of pro-inflammatory cytokines to activate T cells. (Reprint with permission from [58]. Copyright American Chemical Society, 2018)CC BY · PubMed Central
Fig. 3 A typical bottom-up strategy for generating fully artificial exosomes for drug delivery. Hybrid membrane proteins from red blood cells and cancer cells were integrated into liposomes during preparation to form artificial chimeric exosomes (ACEs). ACEs have anti-phagocytosis ability during circulation (from red blood cell) and the tumor-homing ability (from cancer cell) for targeted drug delivery. (Reprinted with permission from Ref. [90]Copyright Royal Society of Chemistry, 2019)
Fig. 3 A typical bottom-up strategy for generating fully artificial exosomes for drug delivery. Hybrid membrane proteins from red blood cells and cancer cells were integrated into liposomes during preparation to form artificial chimeric exosomes (ACEs). ACEs have anti-phagocytosis ability during circulation (from red blood cell) and the tumor-homing ability (from cancer cell) for targeted drug delivery. (Reprinted with permission from Ref. [90]Copyright Royal Society of Chemistry, 2019)CC BY · PubMed Central
Fig. 4 A typical biohybrid strategy for generating hybrid exosomes by freeze-thawing induced fusion for combined tumor chemo-immunotherapy. Genetically engineered exosomes (gExos) were fused with thermosensitive liposomes (TLs) to form hybrid nanoparticles (gETL NPs), which can escape from clearance of mononuclear phagocytic system (MPS) and be activated by hyperthermic intraperitoneal chemotherapy (HIPEC) at the tumor site to release drugs for chemotherapy and polarize tumor-associated macrophages to M2 type to activate T cells for tumor immunotherapy. (Reprinted with permission from Ref [96]. Copyright WILEY–VCH 2020)
Fig. 4 A typical biohybrid strategy for generating hybrid exosomes by freeze-thawing induced fusion for combined tumor chemo-immunotherapy. Genetically engineered exosomes (gExos) were fused with thermosensitive liposomes (TLs) to form hybrid nanoparticles (gETL NPs), which can escape from clearance of mononuclear phagocytic system (MPS) and be activated by hyperthermic intraperitoneal chemotherapy (HIPEC) at the tumor site to release drugs for chemotherapy and polarize tumor-associated macrophages to M2 type to activate T cells for tumor immunotherapy. (Reprinted with permission from Ref [96]. Copyright WILEY–VCH 2020)CC BY · PubMed Central

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Metadata

Authors
Li, Y.-J., Wu, J.-Y., Liu, J., Xu, W., Qiu, X., Huang, S., Hu, X.-B., & Xiang, D.-X.
Venue
Journal of Nanobiotechnology
Publisher
Springer Science and Business Media LLC
Published
2021-08-12
Volume
19
Issue
1
ISSN
1477-3155
DOI
10.1186/s12951-021-00986-2
PMC
PMC8359033
Cited by
303
References
11
Language
en
Licence
Funders
hunan provincial science and technology plan (2016TP2002)

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