Emerging Roles of Using Small Extracellular Vesicles as an Anti-Cancer Drug

Joo, Hyeon Su; Suh, Ju Hun; So, Chan Mi; Jeon, Hye Jin; Yoon, Sol Hee; Lee, Jung Min

doi:10.3390/ijms241814063

IJMS

2023

DOI: 10.3390/ijms241814063

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Emerging Roles of Using Small Extracellular Vesicles as an Anti-Cancer Drug

Hyeon Su Joo,

Ju Hun Suh,

Chan Mi So

et al.

Abstract: Small extracellular vesicles (sEVs) are emerging as a novel therapeutic strategy for cancer therapy. Tumor-cell-derived sEVs contain biomolecules that can be utilized for cancer diagnosis. sEVs can directly exert tumor-killing effects or modulate the tumor microenvironment, leading to anti-cancer effects. In this review, the application of sEVs as a diagnostic tool, drug delivery system, and active pharmaceutical ingredient for cancer therapy will be highlighted. The therapeutic efficacies of sEVs will be comp… Show more

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2024

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Cited by 2 publications

References 138 publications

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Extracellular vesicles and their content in the context of polycystic ovarian syndrome and endometriosis: a review

Duval,

Wyse,

Tsang

et al. 2024

J Ovarian Res

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Extracellular vesicles (EVs), particles enriched in bioactive molecules like proteins, nucleic acids, and lipids, are crucial mediators of intercellular communication and play key roles in various physiological and pathological processes. EVs have been shown to be involved in ovarian follicular function and to be altered in two prevalent gynecological disorders; polycystic ovarian syndrome (PCOS) and endometriosis. Ovarian follicles are complex microenvironments where folliculogenesis takes place with well-orchestrated interactions between granulosa cells, oocytes, and their surrounding stromal cells. Recent research unveiled the presence of EVs, including exosomes and microvesicles, in the follicular fluid (FFEVs), which constitutes part of the developing oocyte’s microenvironment. In the context of PCOS, a multifaceted endocrine, reproductive, and metabolic disorder, studies have explored the dysregulation of these FFEVs and their cargo. Nine PCOS studies were included in this review and two miRNAs were commonly reported in two different studies, miR-379 and miR-200, both known to play a role in female reproduction. Studies have also demonstrated the potential use of EVs as diagnostic tools and treatment options. Endometriosis, another prevalent gynecological disorder characterized by ectopic growth of endometrial-like tissue, has also been linked to aberrant EV signaling. EVs in the peritoneal fluid of women with endometriosis carry molecules that modulate the immune response and promote the establishment and maintenance of endometriosis lesions. EVs derived from endometriosis lesions, serum and peritoneal fluid obtained from patients with endometriosis showed no commonly reported biomolecules between the eleven reviewed studies. Importantly, circulating EVs have been shown to be potential biomarkers, also reflecting the severity of the pathology. Understanding the interplay of EVs within human ovarian follicles may provide valuable insights into the pathophysiology of both PCOS and endometriosis. Targeting EV-mediated communication may open avenues for novel diagnostic and therapeutic approaches for these common gynecological disorders. More research is essential to unravel the mechanisms underlying EV involvement in folliculogenesis and its dysregulation in PCOS and endometriosis, ultimately leading to more effective and personalized interventions.

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Extracellular vesicles and their content in the context of polycystic ovarian syndrome and endometriosis: a review

Duval,

Wyse,

Tsang

et al. 2024

J Ovarian Res

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A Zeolitic Imidazolate Framework-Based Antimicrobial Peptide Delivery System with Enhanced Anticancer Activity and Low Systemic Toxicity

Jiang,

Kaysar,

Pan

et al. 2024

Pharmaceutics

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Background: The clinical efficacies of anticancer drugs are limited by non-selective toxic effects on healthy tissues and low bioavailability in tumor tissue. Therefore, the development of vehicles that can selectively deliver and release drugs at the tumor site is critical for further improvements in patient survival. Methods: We prepared a CEC nano-drug delivery system, CEC@ZIF-8, with a zeolite imidazole framework-8 (ZIF-8) as a carrier, which can achieve the response of folate receptor (FR). We characterized this system in terms of morphology, particle size, zeta potential, infrared (IR), x-ray diffraction (XRD), and transcriptome analysis, and examined the in vitro cytotoxicity and cellular uptake properties of CEC@ZIF-8 using cervical cancer cells. Lastly, we established a TC-1 tumor-bearing mouse model and evaluated its in vivo anti-cervical cancer activity. Results: The CEC@ZIF-8 nano-delivery system had favorable biocompatibility, heat stability, and pH responsiveness, with a CEC loading efficiency of 12%, a hydrated particle size of 174 ± 5.8 nm, a zeta potential of 20.57 mV, and slow and massive drug release in an acidic environment (pH 5.5), whereas release was 6% in a neutral environment (pH 7.4). At the same time, confocal imaging and cell viability assays demonstrated greater intracellular accumulation and more potent cytotoxicity against cancer cells compared to free CEC. The mechanism was analyzed by a series of transcriptome analyses, which revealed that CEC@ZIF-8 NPs differentially regulate the expression levels of 1057 genes in cancer cells, and indicated that the enriched pathways were mainly cell cycle and apoptosis-related pathways via the enrichment analysis of the differential genes. Flow cytometry showed that CEC@ZIF-8 NPs inhibited the growth of HeLa cells by arresting the cell cycle at the G0/G1 phase. Flow cytometry also revealed that CEC@ZIF-8 NPs induced greater apoptosis rates than CEC, while unloaded ZIF-8 had little inherent pro-apoptotic activity. Furthermore, the levels of reactive oxygen species (ROS) were also upregulated by CEC@ZIF-8 NPs while ROS inhibitors and caspase inhibitors reversed CEC@ZIF-8 NPs-induced apoptosis. Finally, CEC@ZIF-8 NPs also reduced the growth rate of xenograft tumors in mice without the systemic toxicity observed with cisplatin treatment. Conclusions: The CEC@ZIF-8 nano-drug delivery system significantly enhanced the anti-cervical cancer effect of CEC both in vivo and in vitro, providing a more promising drug delivery system for clinical applications and tumor management. At the same time, this work demonstrates the clinical potential of CEC-loaded ZIF-8 nanoparticles for the selective destruction of tumor tissues.

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Emerging Roles of Using Small Extracellular Vesicles as an Anti-Cancer Drug

Cited by 2 publications

References 138 publications

Extracellular vesicles and their content in the context of polycystic ovarian syndrome and endometriosis: a review

Extracellular vesicles and their content in the context of polycystic ovarian syndrome and endometriosis: a review

A Zeolitic Imidazolate Framework-Based Antimicrobial Peptide Delivery System with Enhanced Anticancer Activity and Low Systemic Toxicity

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