Progress in extracellular vesicle biology and their application in cancer medicine

Srivastava, Akhil; Amreddy, Narsireddy; Pareek, Vipul; Chinnappan, Mahendran; Ahmed, Rebaz; Mehta, Meghna; Razaq, Mohammad; Munshi, Anupama; Ramesh, Rajagopal

doi:10.1002/wnan.1621

Cited by 43 publications

(41 citation statements)

References 117 publications

(133 reference statements)

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“…The most common approaches include opening up the pores in lipid membranes by physic forces, such as electroporation, sonication, freeze and thaw cycles, and extrusion, and by chemical means, such as using transfection reagents. The pros and cons of these methods for membrane permeabilization and cargo loading has been reviewed elsewhere [ 147 ]. Therefore, we will only briefly discuss these loading approaches in the following.…”

Section: Evs As Drug Carriers In Cancer Treatmentmentioning

confidence: 99%

Extracellular Vesicles in the Development of Cancer Therapeutics

Sun

Burrola

et al. 2020

IJMS

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Extracellular vesicles (EVs) are small lipid bilayer-delimited nanoparticles released from all types of cells examined thus far. Several groups of EVs, including exosomes, microvesicles, and apoptotic bodies, have been identified according to their size and biogenesis. With extensive investigations on EVs over the last decade, it is now recognized that EVs play a pleiotropic role in various physiological processes as well as pathological conditions through mediating intercellular communication. Most notably, EVs have been shown to be involved in cancer initiation and progression and EV signaling in cancer are viewed as potential therapeutic targets. Furthermore, as membrane nanoparticles, EVs are natural products with some of them, such as tumor exosomes, possessing tumor homing propensity, thus leading to strategies utilizing EVs as drug carriers to effectively deliver cancer therapeutics. In this review, we summarize recent reports on exploring EVs signaling as potential therapeutic targets in cancer as well as on developing EVs as therapeutic delivery carriers for cancer therapy. Findings from preclinical studies are primarily discussed, with early phase clinical trials reviewed. We hope to provide readers updated information on the development of EVs as cancer therapeutic targets or therapeutic carriers.

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Section: Evs As Drug Carriers In Cancer Treatmentmentioning

confidence: 99%

Extracellular Vesicles in the Development of Cancer Therapeutics

Sun

Burrola

et al. 2020

IJMS

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“…Even exogenous loading of small mRNA molecules into EVs is a complicated challenge which needs to be overcome [ 22 ]. This technique represents loading big molecules, rather than encapsulation, as described by Srivastava, A. et al and it differs from the others by this aspect [ 33 ]. Therefore, cell culture and drug release studies proved that DOX amount could be loaded successfully and molecular function was not diminished in the ultrasonication process.…”

Section: Discussionmentioning

confidence: 99%

Efficient Doxorubicin Loading to Isolated Dexosomes of Immature JAWSII Cells: Formulated and Characterized as the Bionanomaterial

et al. 2020

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Immature dendritic cells (IDc), ‘dexosomes’, are promising natural nanomaterials for cancer diagnose and therapy. Dexosomes were isolated purely from small-scale-up production by using t25-cell-culture flasks. Total RNA was measured as 1.43 ± 0.33 ng/106 cell. Despite the fact that they possessed a surface that is highly abundant in protein, this did not become a significant effect on the DOX loading amount. Ultrasonication was used for doxorubicin (DOX) loading into the IDc dexosomes. In accordance with the literature, three candidate DOX formulations were designed as IC50 values; dExoIII, 1.8 µg/mL, dExoII, 1.2 µg/mL, and dExoI, 0.6 µg/mL, respectively. Formulations were evaluated by MTT test against highly metastatic A549 (CCL-185; ATTC) cell line. Confocal images of unloaded (naïve) were obtained by CellMaskTM membrane staining before DOX loading. Although, dexosome membranes were highly durable subsequent to ultrasonication, it was observed that dexosomes could not be stable above 70 °C during the SEM-image analyses. dExoIII displayed sustained release profile. It was found that dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA) results were in good agreement with each other. Zeta potentials of loaded dexosomes have approximately between −15 to −20 mV; and, their sizes are 150 nm even after ultrasonication. IDcJAWSII dexosomes can be able to be utilized as the “BioNanoMaterial” after DOX loading via ultrasonication technique.

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“…The nomenclature of these vesicles evolved during the last two decades [ 9 ]. The widespread and oldest classification divides the EVs on the base of their biogenetic pathway and, even simplistically, identifies three main classes: the exosomes, the microvesicles, and the apoptotic bodies ( Figure 1 ).…”

Section: Natural Evsmentioning

confidence: 99%

“…Their surface can be modified with various macromolecules, including peptides, dyes, or stealth polymers for diagnostic purposes; cell tracking; or even for targeting other cells or tissues [ 5 ]. EVs have shown to have a role in the immune system modulation or as promoters of carcinogenicity [ 4 , 5 , 8 , 9 ]. They have been recently shown to coat both organic and inorganic nanoparticles, thus producing novel biomimetic hybrids [ 6 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

“…EVs have shown to have a role in the immune system modulation or as promoters of carcinogenicity [ 4 , 5 , 8 , 9 ]. They have been recently shown to coat both organic and inorganic nanoparticles, thus producing novel biomimetic hybrids [ 6 , 9 ]. Therefore, they are becoming the invisible warriors of today’s nanomedicine, the camouflage suit for many devices and drugs [ 7 , 10 , 11 , 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

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EVs and Bioengineering: From Cellular Products to Engineered Nanomachines

Villata

Canta

Cauda

2020

IJMS

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Extracellular vesicles (EVs) are natural carriers produced by many different cell types that have a plethora of functions and roles that are still under discovery. This review aims to be a compendium on the current advancement in terms of EV modifications and re-engineering, as well as their potential use in nanomedicine. In particular, the latest advancements on artificial EVs are discussed, with these being the frontier of nanomedicine-based therapeutics. The first part of this review gives an overview of the EVs naturally produced by cells and their extraction methods, focusing on the possibility to use them to carry desired cargo. The main issues for the production of the EV-based carriers are addressed, and several examples of the techniques used to upload the cargo are provided. The second part focuses on the engineered EVs, obtained through surface modification, both using direct and indirect methods, i.e., engineering of the parental cells. Several examples of the current literature are proposed to show the broad variety of engineered EVs produced thus far. In particular, we also report the possibility to engineer the parental cells to produce cargo-loaded EVs or EVs displaying specific surface markers. The third and last part focuses on the most recent advancements based on synthetic and chimeric EVs and the methods for their production. Both top-down or bottom-up techniques are analyzed, with many examples of applications.

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Progress in extracellular vesicle biology and their application in cancer medicine

Cited by 43 publications

References 117 publications

Extracellular Vesicles in the Development of Cancer Therapeutics

Extracellular Vesicles in the Development of Cancer Therapeutics

Efficient Doxorubicin Loading to Isolated Dexosomes of Immature JAWSII Cells: Formulated and Characterized as the Bionanomaterial

EVs and Bioengineering: From Cellular Products to Engineered Nanomachines

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