Doxorubicin-loaded cell-derived nanovesicles: an alternative targeted approach for anti-tumor therapy

Goh, Wei Jiang; Lee, Choon Keong; Zou, Shui; Woon, Esther C. Y.; Czarny, Bertrand; Pastorin, Giorgia

doi:10.2147/ijn.s131786

Cited by 84 publications

(74 citation statements)

References 17 publications

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“…International Publisher blood, biomolecules in exosomes are well protected and concentrated [7,8]. In recent years, cancer exosomes have been explored for their important role in tumor progression, especially inflammatory response, formation of pre-metastatic niche, and organotropism that play key roles in cancer metastasis [9][10][11][12].…”

Section: Ivyspringmentioning

confidence: 99%

Functional Passenger-Strand miRNAs in Exosomes Derived from Human Colon Cancer Cells and Their Heterogeneous Paracrine Effects

Gao¹,

Lei²,

Zeng³

et al. 2020

Int. J. Biol. Sci.

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Exosome-mediated microRNAs (miRNAs) are closely related to the occurrence, development, invasion, metastasis, therapeutic resistance, diagnosis and treatment of malignant tumors. Guide-strand miRNA and passenger-strand miRNA (miRNA*) exist in miRNA processing, but the function of passenger-strand miRNA is often overlooked. In this study, we attempted to identify functional miRNA*s in exosomes derived from human colon cancer SW620 cells. miRNA expression profiles of human normal colonic epithelial cells NCM460 and colon cancer cells SW620 were compared by high-throughput sequencing. According to the sequencing results, we defined two sets of differentially expressed miRNAs: "high in exosome and high in cell" (HEHC) and "high in exosome but low in cell" (HELC). As passenger-strand miRNAs, miR-2277-3p and miR-26b-3p, which belong to different sets, have diametrically opposite functions. MiR-2277-3p promotes proliferation, migration, and invasion of SW620 cells by targeting NUPR1L, while miR-26b-3p exerts an inhibitory effect by targeting PFDN1. Using exosomes as transport vectors, the effect of exosomes rich in miR-2277-3p on cells is consistent with the effect of liposome-transfected overexpressed miR-2277-3p, resulting in a cancer-promoting effect. However, exosomes rich in miR-26b-3p did not have a tumor suppressor effect. Further analysis revealed that exosomes rich in miR-2277-3p also had a high abundance of integrin β4. Altering the abundance of integrin β4 in exosomes changes the ability of exosomes to be taken up by cells, thereby altering the paracrine effects of exosomes. In summary, we revealed the fact that a large number of passenger-strand miRNAs exist in exosomes of colon cancer cells, these miRNAs are preliminarily categorized into two sets, and miR-2277-3p and miR-26b-3p, as representatives of each set, showed opposite functions. In addition, we revealed that integrin β4 is a marker of exosome heterogeneity in colon cancer cells, which directly correlates with the ability of exosomes to be uptaken by cells of the same kind, thus regulating the paracrine effect of exosomes.

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Section: Ivyspringmentioning

confidence: 99%

Functional Passenger-Strand miRNAs in Exosomes Derived from Human Colon Cancer Cells and Their Heterogeneous Paracrine Effects

Gao¹,

Lei²,

Zeng³

et al. 2020

Int. J. Biol. Sci.

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“…The highest Dox loading was observed by incubation at RT, followed by the saponification and freeze–thaw methods. Dox-loaded EVs showed higher cytotoxicity against both cancer and normal cells after incubation at 37 °C for 5 min compared to the free drug [ 81 ].…”

Section: Drug Loading Into Evs and Evmsmentioning

confidence: 99%

“…Compared to other methods, incubation does not affect the size and morphology of EVs. However, one disadvantage is its lack of drug-loading capacity [ 73 , 79 , 80 , 81 , 88 ].…”

Section: Advantages and Disadvantages Of Ev- And Evm-based Drug Lomentioning

confidence: 99%

Extracellular Vesicle- and Extracellular Vesicle Mimetics-Based Drug Delivery Systems: New Perspectives, Challenges, and Clinical Developments

Gangadaran

Ahn

2020

Pharmaceutics

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Extracellular vesicles (EVs) are small membrane-based nanovesicles naturally released from cells. Extracellular vesicles mimetics (EVMs) are artificial vesicles engineered from cells or in combination with lipid materials, and they mimic certain characteristics of EVs. As such, EVs facilitate intracellular communication by carrying and delivering biological materials, such as proteins, lipids, and nucleic acids, and they have been found to find organ tropism in preclinical studies. Because of their native structure and characteristics, they are considered promising drug carriers for future clinical use. This review outlines the origin and composition of natural EVs and EVM engineering and internalization. It then details different loading approaches, with examples of the drug delivery of therapeutic molecules. In addition, the advantages and disadvantages of loading drugs into EVs or EVMs as a drug delivery system are discussed. Finally, the advantages of EVMs over EVs and the future clinical translation of EVM-based drug delivery platforms are outlined.

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“…This method shows lower cargo loading compared to sonication- and extrusion-based methods [ 155 ]. One to three cycles of freeze and thaw were usually performed during drug incorporation, which may accelerate the degradation and aggregation of the sEVs [ 122 , 156 ].…”

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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Doxorubicin-loaded cell-derived nanovesicles: an alternative targeted approach for anti-tumor therapy

Cited by 84 publications

References 17 publications

Functional Passenger-Strand miRNAs in Exosomes Derived from Human Colon Cancer Cells and Their Heterogeneous Paracrine Effects

Functional Passenger-Strand miRNAs in Exosomes Derived from Human Colon Cancer Cells and Their Heterogeneous Paracrine Effects

Extracellular Vesicle- and Extracellular Vesicle Mimetics-Based Drug Delivery Systems: New Perspectives, Challenges, and Clinical Developments

Extracellular Vesicles in the Development of Cancer Therapeutics

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