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Review
. 2021 Feb 8:10:606906.
doi: 10.3389/fonc.2020.606906. eCollection 2020.

Extracellular Vesicles: An Emerging Nanoplatform for Cancer Therapy

Yifan Ma  1 , Shiyan Dong  2   3 , Xuefeng Li  4 , Betty Y S Kim  5 , Zhaogang Yang  2 , Wen Jiang  2
Affiliations
Review

Extracellular Vesicles: An Emerging Nanoplatform for Cancer Therapy

Yifan Ma et al. Front Oncol. .

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.

Keywords: cancer therapy; drug delivery; exosome; extracellular vesicle; therapeutic nanoplatform.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
A schematic of EV’s role in cancer development and progression (31) (with reproduction permission).
Figure 2
Figure 2
A schematic of EVs engineering strategies that is categorized into two groups: direct extracellular modification and indirect intracellular modification.
Figure 3
Figure 3
(A) Optimized electroporation parameters for direct EVs loading were screened including voltages and pulses. When the desired cargos were miRNAs, 750 V and 10 pulses showed the most significant miRNA enrichment (66). (B) A novel tumor-cell-exocytosed exosome-biomimetic porous silicon nanoparticles (PSiNPs) was developed through the incubation of the synthetic nanoparticles with parent cells. Such engineered exosomes significantly increased DOX loading and improved antitumor efficacy (67). (C) An exosomal transfer into cells (EXOtic) device enables exosome mass production and efficient exosomal mRNA delivery (68). (D) A cellular nanoporation (CNP) technology trigger a 50-fold increase of exosomes yield and thousand-fold increase of mRNA transcripts in the released exosomes from CNP-transfected cells release (69) (with reproduction permission).
Figure 4
Figure 4
(A) EVs elicited from two cytotoxic drugs, taxanes and anthracyclines, were found to enhance the pro-metastatic ability in mouse (a) and zebrafish (b) tumor models (90). (B) EVs collected from activated CD8+ T cells were found to be actively involved in interrupting fibroblastic stroma-mediated tumor progression by depleting tumor mesenchymal cells (91). (C) Molecular profile of radiation-derived exosomes demonstrated that radiation increased the exosomal proteins related to tumor migration and progression (92) (with reproduction permission).
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