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Advances in Exosome-Based Drug Delivery and Tumor Targeting: From Tissue Distribution to Intracellular Fate

Shao, Juntang, Zaro, Jennica, Shen, Yuxian·2020·International Journal of Nanomedicine
DOI 10.2147/ijn.s281890PMC PMC7700079
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Figure 1 Graphical illustration of tumor targeting strategies of exosome-based delivery. In passive targeting, exosomes pass through the leaky vascular walls and accumulate at the tumor site by the enhanced permeability and retention (EPR) effect. The EPR effect is boosted by (A) increasing endothelial penetration of tumor vasculature by surface modification of iRGD peptide;80 and (B) prolonging circulation time of exosomes by overexpressing antiphagocytic factors.17 In addition, reshaping tumor microenvironment (TME) by targeting specific immune cells could enhance anti-tumor immune responses for cancer immunotherapy. For example, (C) exosome expressing in-tandem scFvs (anti-EGFR and anti-CD3) redirect cytotoxic T cells to attack tumor cells;84 and (D) glycan-modified exosomes displayed increased uptake by DC cells and augment DC-mediated immune responses.86 Active targeting can be achieved (E) by using specific targeting moiety to bind to the receptors on tumor cells or by modification to synergize external stimuli-guided tumor targeting.93,95,101,102,105.
Figure 1 Graphical illustration of tumor targeting strategies of exosome-based delivery. In passive targeting, exosomes pass through the leaky vascular walls and accumulate at the tumor site by the enhanced permeability and retention (EPR) effect. The EPR effect is boosted by (A) increasing endothelial penetration of tumor vasculature by surface modification of iRGD peptide;80 and (B) prolonging circulation time of exosomes by overexpressing antiphagocytic factors.17 In addition, reshaping tumor microenvironment (TME) by targeting specific immune cells could enhance anti-tumor immune responses for cancer immunotherapy. For example, (C) exosome expressing in-tandem scFvs (anti-EGFR and anti-CD3) redirect cytotoxic T cells to attack tumor cells;84 and (D) glycan-modified exosomes displayed increased uptake by DC cells and augment DC-mediated immune responses.86 Active targeting can be achieved (E) by using specific targeting moiety to bind to the receptors on tumor cells or by modification to synergize external stimuli-guided tumor targeting.93,95,101,102,105.CC BY-NC · PubMed Central
Figure 2 Graphical illustration of approaches to enhance intracellular payload delivery. Cell uptake of exosomes is mediated by several means, including endocytosis, phagocytosis, and direct fusion with plasma membrane. Intracellular payload delivery can be enhanced by several approaches, including: (A) modifying exosomes with cell-penetrating peptides (eg, arginine-rich peptide) to stimulate cell micropinocytosis; Promoting exosome-cell fusion by (B) increasing membrane rigidity of exosome via enriched sphingolipid and cholesterol;67 or by (C) expressing VSV-G on exosome to aid membrane fusion.107 (D) Exosomes expressing connexin-43 that forms hexametric channels to allow exosome to dock to gap junction pore on plasma membrane and, therefore, enable direct cytoplasmic transfer of cargo.108 In addition, (E) integrating fusogenic peptide (eg, GALA peptide) facilitates exosome escape of payload before lysosomal degradation.109
Figure 2 Graphical illustration of approaches to enhance intracellular payload delivery. Cell uptake of exosomes is mediated by several means, including endocytosis, phagocytosis, and direct fusion with plasma membrane. Intracellular payload delivery can be enhanced by several approaches, including: (A) modifying exosomes with cell-penetrating peptides (eg, arginine-rich peptide) to stimulate cell micropinocytosis; Promoting exosome-cell fusion by (B) increasing membrane rigidity of exosome via enriched sphingolipid and cholesterol;67 or by (C) expressing VSV-G on exosome to aid membrane fusion.107 (D) Exosomes expressing connexin-43 that forms hexametric channels to allow exosome to dock to gap junction pore on plasma membrane and, therefore, enable direct cytoplasmic transfer of cargo.108 In addition, (E) integrating fusogenic peptide (eg, GALA peptide) facilitates exosome escape of payload before lysosomal degradation.109CC BY-NC · PubMed Central

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Metadata

Authors
Shao, J., Zaro, J., & Shen, Y.
Venue
International Journal of Nanomedicine
Publisher
Informa UK Limited
Published
2020-11
Volume
Volume 15
Pages
9355-9371
ISSN
1178-2013
DOI
10.2147/ijn.s281890
PMC
PMC7700079
Cited by
295
References
19
Language
en
Licence
creativecommons.org/licenses/by-nc/3.0/ (unspecified)

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Shao, J., Zaro, J., & Shen, Y. (2020). Advances in Exosome-Based Drug Delivery and Tumor Targeting: From Tissue Distribution to Intracellular Fate. International Journal of Nanomedicine. https://doi.org/10.2147/ijn.s281890