Extracellular vesicles as natural therapeutic agents and innate drug delivery systems for cancer treatment: Recent advances, current obstacles, and challenges for clinical translation

Pirisinu, Marco; Pham, Tin Chanh; Zhang, Daniel Xin; Hong, Tran Nguyen; Nguyen, Lap Thi; Le, Minh Tn

doi:10.1016/j.semcancer.2020.08.007

Cited by 67 publications

(56 citation statements)

References 253 publications

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“…At present, preclinical studies on oligonucleotide administration for cancer treatments mainly utilize EVs as a delivery system, obtaining them from therapeutically irrelevant engineered cells [ 25 ]. For instance, breast tumor cells were engineered with tumor suppressor miR-134 and let-7 and the deriving EVs were shown to display potent anti-tumor effects [ 26 , 27 ].…”

Section: Discussionmentioning

confidence: 99%

Coincubation as miR-Loading Strategy to Improve the Anti-Tumor Effect of Stem Cell-Derived EVs

et al. 2021

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Extracellular vesicles are considered a novel therapeutic tool, due to their ability to transfer their cargoes to target cells. Different strategies to directly load extracellular vesicles with RNA species have been proposed. Electroporation has been used for the loading of non-active vesicles; however, the engineering of vesicles already carrying a therapeutically active cargo is still under investigation. Here, we set up a coincubation method to increase the anti-tumor effect of extracellular vesicles isolated from human liver stem cells (HLSC-EVs). Using the coincubation protocol, vesicles were loaded with the anti-tumor miRNA-145, and their effect was evaluated on renal cancer stem cell invasion. Loaded HLSC-EVs maintained their integrity and miR transfer ability. Loaded miR-145, but not miR-145 alone, was protected by RNAse digestion, possibly due to its binding to RNA-binding proteins on HLSC-EV surface, such as Annexin A2. Moreover, miR-145 coincubated HLSC-EVs were more effective in inhibiting the invasive properties of cancer stem cells, in comparison to naïve vesicles. The protocol reported here exploits a well described property of extracellular vesicles to bind nucleic acids on their surface and protect them from degradation, in order to obtain an effective miRNA loading, thus increasing the activity of therapeutically active naïve extracellular vesicles.

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Section: Discussionmentioning

confidence: 99%

Coincubation as miR-Loading Strategy to Improve the Anti-Tumor Effect of Stem Cell-Derived EVs

et al. 2021

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“…The use of EVs is currently being evaluated as a therapeutic strategy for treatment of variety of diseases including cancers (Pirisinu et al., 2020; Walker et al., 2019), cardiovascular diseases (De Abreu et al., 2020), neurogenerative diseases (Ferrantelli et al., 2020) and diabetes (Noren Hooten & Evans, 2020; Xiao et al., 2019). Many of these pre‐clinical studies have shown promise in in vivo models and use EVs to deliver specific cargo such as miRNAs, siRNAs and proteins.…”

Section: Why Are Evs Advantageous As Therapeutics?mentioning

confidence: 99%

“…An IL‐16 domain fused to Lamp2b targets EVs to CD4 + T cells (Tang et al., 2018). Lamp2b is of course not the only EV protein that can be used, and other strategies for targeting have also been employed (Pirisinu et al., 2020; Walker et al., 2019). Other approaches to modify EVs and increase their affinity for selective organs could also be considered (reviewed in (Murphy et al., 2019)), including the use of aptamers (Hosseini Shamili et al., 2019; Wang et al., 2017).…”

Section: Targeting and Selective Retentionmentioning

confidence: 99%

“…Additionally, EVs are ‘targetable’. Display of specific proteins, and possibly other biomolecules, allows EVs to be sorted to certain cell types and tissues or away from undesired recipients (Ferrantelli, Chiozzini, Leone, Manfredi, & Federico, 2020; Pirisinu et al., 2020; Walker et al., 2019). EV engineering, by manipulating the EV source or by altering EVs post‐production, can be used to enhance such targeting.…”

Section: Introductionmentioning

confidence: 99%

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Hitting the Bullseye: Are extracellular vesicles on target?

Hooten

Yáñez-Mó

DeRita

et al. 2020

J of Extracellular Vesicle

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“…Recent reviews on exosomes have focused on therapeutic efficacy of exosomes by addressing extracellular vesicular interaction with the host immune system [ 14 ], constraints and opportunities available with bioengineering of exosomes [ 15 , 16 , 17 ], success against multiple cancers [ 18 ] and exosome-based drug delivery [ 19 , 20 , 21 ]. Anticancer treatments sometimes experience shortfall in their efficacy due to unwanted side effects of the therapeutic agents or shortened shelf-life, but exosomes serve as natural agents to overcome these issues and become a potent therapeutic agent [ 22 ]. However, instead of perceiving specific therapeutic potential of exosomes, the present review has tried to decipher the entire repertoire of exosomes, including both protumorigenic and antitumorigenic impact.…”

Section: Introductionmentioning

confidence: 99%

Trends in Research on Exosomes in Cancer Progression and Anticancer Therapy

Sinha

Roy

Saha

et al. 2021

Cancers

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Exosomes, the endosome-derived bilayered extracellular nanovesicles with their contribution in many aspects of cancer biology, have become one of the prime foci of research. Exosomes derived from various cells carry cargoes similar to their originator cells and their mode of generation is different compared to other extracellular vesicles. This review has tried to cover all aspects of exosome biogenesis, including cargo, Rab-dependent and Rab-independent secretion of endosomes and exosomal internalization. The bioactive molecules of the tumor-derived exosomes, by virtue of their ubiquitous presence and small size, can migrate to distal parts and propagate oncogenic signaling and epigenetic regulation, modulate tumor microenvironment and facilitate immune escape, tumor progression and drug resistance responsible for cancer progression. Strategies improvised against tumor-derived exosomes include suppression of exosome uptake, modulation of exosomal cargo and removal of exosomes. Apart from the protumorigenic role, exosomal cargoes have been selectively manipulated for diagnosis, immune therapy, vaccine development, RNA therapy, stem cell therapy, drug delivery and reversal of chemoresistance against cancer. However, several challenges, including in-depth knowledge of exosome biogenesis and protein sorting, perfect and pure isolation of exosomes, large-scale production, better loading efficiency, and targeted delivery of exosomes, have to be confronted before the successful implementation of exosomes becomes possible for the diagnosis and therapy of cancer.

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Extracellular vesicles as natural therapeutic agents and innate drug delivery systems for cancer treatment: Recent advances, current obstacles, and challenges for clinical translation

Cited by 67 publications

References 253 publications

Coincubation as miR-Loading Strategy to Improve the Anti-Tumor Effect of Stem Cell-Derived EVs

Coincubation as miR-Loading Strategy to Improve the Anti-Tumor Effect of Stem Cell-Derived EVs

Hitting the Bullseye: Are extracellular vesicles on target?

Trends in Research on Exosomes in Cancer Progression and Anticancer Therapy

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