Liposomal Delivery of MicroRNA-7 Targeting EGFR to Inhibit the Growth, Invasion, and Migration of Ovarian Cancer

Cui, Xiaojuan; Song, Keqi; Lu, Xiaolan; Feng, Weiwei; Di, Wen

doi:10.1021/acsomega.1c00992

Cited by 20 publications

(18 citation statements)

References 38 publications

(74 reference statements)

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“…Together our study unravels an interesting aspect that despite multiple predicted targets for miRNA, only a few targets are significantly altered which may contribute to the overall phenotype. However, this also suggests that the idea to use miRNA-7 as a potential anti-cancer therapeutic 26 may have to be carefully determined given the adverse remodeling observed with cardiomyocyte expression of miRNA-7, an observation reminiscent of anthracycline mediated cardiotoxicity.…”

Section: Discussionmentioning

confidence: 99%

Cardiac expression of microRNA-7 is associated with adverse cardiac remodeling

Gupta

Sahu

Sun

et al. 2021

Sci Rep

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Although microRNA-7 (miRNA-7) is known to regulate proliferation of cancer cells by targeting Epidermal growth factor receptor (EGFR/ERBB) family, less is known about its role in cardiac physiology. Transgenic (Tg) mouse with cardiomyocyte-specific overexpression of miRNA-7 was generated to determine its role in cardiac physiology and pathology. Echocardiography on the miRNA-7 Tg mice showed cardiac dilation instead of age-associated physiological cardiac hypertrophy observed in non-Tg control mice. Subjecting miRNA-7 Tg mice to transverse aortic constriction (TAC) resulted in cardiac dilation associated with increased fibrosis bypassing the adaptive cardiac hypertrophic response to TAC. miRNA-7 expression in cardiomyocytes resulted in significant loss of ERBB2 expression with no changes in ERBB1 (EGFR). Cardiac proteomics in the miRNA-7 Tg mice showed significant reduction in mitochondrial membrane structural proteins compared to NTg reflecting role of miRNA-7 beyond the regulation of EGFR/ERRB in mediating cardiac dilation. Consistently, electron microscopy showed that miRNA-7 Tg hearts had disorganized rounded mitochondria that was associated with mitochondrial dysfunction. These findings show that expression of miRNA-7 in the cardiomyocytes results in cardiac dilation instead of adaptive hypertrophic response during aging or to TAC providing insights on yet to be understood role of miRNA-7 in cardiac function.

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Section: Discussionmentioning

confidence: 99%

Cardiac expression of microRNA-7 is associated with adverse cardiac remodeling

Gupta

Sahu

Sun

et al. 2021

Sci Rep

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“…Similarly, modified and unmodified LNPs have been used to deliver miRNA previously. Cationic liposomes have been used as transfection agents to deliver miRNA such as miR-7 to ovarian cancer cells, miR-143 and -145 in human colorectal tumors, and miR-122 in liver cells achieving up to 80% efficiency [86,124,125]. Cationic liposomes typically consist of a cationic lipid, neutral lipid and/or cholesterol, and a PEG-lipid.…”

Section: Discussionmentioning

confidence: 99%

“…The miRNA uptake's temporal efficiency depends on the miRNA endocytotic mechanism, the miRNA carrier vehicle, and the miRNA type [86,87]. For example, the miRNA uptake of a human ovarian cancer cell line treated with liposomes loaded with fluorescently-labeled hsa-miR-7-5p increased linearly over 24 hours [86]. The uptake of miRNA in multiple myeloma treated with stable nucleic acid-lipid particles (SNALPs) loaded with hsa-miR-34a decreased after 48 hours [87].…”

Section: The Dynamic Light Scattering (Dls) Technique Reveals How Different Processes Affect Vesicle Sizementioning

confidence: 99%

Section: The Dynamic Light Scattering (Dls) Technique Reveals How Different Processes Affect Vesicle Sizementioning

confidence: 99%

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A novel method for producing functionalized vesicles that efficiently deliver oligonucleotides in vitro in cancer cells and in vivo in mice

Roberts

Jain

2021

Preprint

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Nano-based delivery systems have greatly enhanced our ability to administer and target drugs and macromolecules to their therapeutic targets. Because of chemically modifying them and their functional effects on cells, oligonucleotide drugs have great therapeutic potential. Oligonucleotide drugs have off-target effects and stability issues, so they can be encapsulated functionalized vesicles with targeting ligands such as antibodies (Ab). Herein, we describe a novel, scalable and straightforward approach to produce functionalized vesicles, which we call the Functionalized Lipid Insertion Method. This method differs significantly from an older approach for producing functionalized vesicles referred to as the Detergent-Dialysis Method. The older method requires excess detergent and extensive dialysis over many hours to produce the functionalized vesicles. With the Functionalized Lipid Insertion Method, only the functionalized lipid is detergent-solubilized during the formation of the functionalized vesicle. The approach reduces the dialysis time, keeps the vesicle intact, and orients the functionalized lipid to improve targeting compared to the older method. The dynamic light scattering (DLS) technique demonstrates that vesicle size is sensitive to the initial solubilized component mixture by the older method. In contrast, functionalized vesicle size increases in size are consistent with functionalized lipid insertion into the vesicle. In vitro, functionalized vesicles using our approach are able to deliver oligonucleotides selectively and can functionally affect liver cancer HepG2 cells. Functionalized vesicles produced by this method can also achieve targeted delivery of oligonucleotides in mice without inducing a significant immune response through cytokine production or showing physical signs of an immune response. The industrial and therapeutic significance and implications of functionalized vesicles produced by our method are also discussed.

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“…Yan et al showed that miR-203-loaded liposomes silence slug expression in vitro and in vivo, inhibit the TGF-β1/Smad pathway in triple-negative breast cancer cells, and improve the anticancer effects of chemotherapy [91]. miR-7-loaded cationic liposomes inhibit epidermal growth factor receptor (EGFR) and suppress the spread of ovarian cancer [92]. Moreover, Zhang et al reported that transferrin-targeted miR-221 inhibitor-loaded liposomes show a 15-fold higher delivery to HepG2 cells than nontargeted liposomes and increase the expression levels of miR-221 targets, suggesting efficient delivery [93].…”

Section: Cell-based Delivery Systemsmentioning

confidence: 99%

The Challenges and Opportunities in the Development of MicroRNA Therapeutics: A Multidisciplinary Viewpoint

Momin

Gaddam

Kravitz

et al. 2021

Cells

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microRNAs (miRs) are emerging as attractive therapeutic targets because of their small size, specific targetability, and critical role in disease pathogenesis. However, <20 miR targeting molecules have entered clinical trials, and none progressed to phase III. The difficulties in miR target identification, the moderate efficacy of miR inhibitors, cell type-specific delivery, and adverse outcomes have impeded the development of miR therapeutics. These hurdles are rooted in the functional complexity of miR’s role in disease and sequence complementarity-dependent/-independent effects in nontarget tissues. The advances in understanding miR’s role in disease, the development of efficient miR inhibitors, and innovative delivery approaches have helped resolve some of these hurdles. In this review, we provide a multidisciplinary viewpoint on the challenges and opportunities in the development of miR therapeutics.

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Liposomal Delivery of MicroRNA-7 Targeting EGFR to Inhibit the Growth, Invasion, and Migration of Ovarian Cancer

Cited by 20 publications

References 38 publications

Cardiac expression of microRNA-7 is associated with adverse cardiac remodeling

Cardiac expression of microRNA-7 is associated with adverse cardiac remodeling

A novel method for producing functionalized vesicles that efficiently deliver oligonucleotides in vitro in cancer cells and in vivo in mice

The Challenges and Opportunities in the Development of MicroRNA Therapeutics: A Multidisciplinary Viewpoint

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