Aptamer-mediated gene therapy enhanced antitumor activity against human hepatocellular carcinoma in vitro and in vivo

Xiao, Shuangli; Liu, Zhongbing; Deng, Ruolan; Li, Chunhong; Fu, Shaozhi; Chen, Guilan; Zhang, Xiaoqin; Ke, Famin; Ke, Siyun; Yu, Xin; Wang, Shurong; Zhong, Zhaohui

doi:10.1016/j.jconrel.2017.05.017

Cited by 27 publications

(19 citation statements)

References 33 publications

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“…This method significantly inhibited cell proliferation and cell migration in HepG2 with no toxic effect observed in healthy liver cells. Moreover, it induced cell apoptosis in aggressive HepG2 xenograft in nude mice without concentration-dependent toxicity [ 81 ].…”

Section: Development Of Aptamer Against Hccmentioning

confidence: 99%

Aptamer: A potential oligonucleotide nanomedicine in the diagnosis and treatment of hepatocellular carcinoma

et al. 2017

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Hepatocellular carcinoma (HCC) is one of the most common cancers with a high mortality rate. Late diagnosis and poor prognosis are still a major drawback since curative therapies such as liver resection and liver transplantation are effective only for an early stage HCC. Development of novel molecular targeting therapies against HCC may provide new options that will improve the efficiency of the diagnosis and the success of the therapy, thus ameliorating the life expectancy of the patients. The aptamer is an oligonucleotide nanomedicine that has high binding affinity and specificity to small and large target molecules in the intracellular and extracellular environment with agonist or antagonist function. Currently, several aptamers for diagnostic and therapeutic purposes are under development to recognize different molecules of HCC. In in vitro models, the aptamer has been shown to be able to reduce the growth of HCC cells and increase the sensitivity to conventional chemotherapies. In in vivo mouse models, aptamer could induce cell apoptosis with antitumor activity. Overall data had shown that aptamer has limited toxicity and might be safe in clinical application. This review summarizes recent information of aptamer as a potential oligonucleotide nanomedicine tool, in diagnostics, targeted therapy, and as drug delivery nano-vehicles.

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Section: Development Of Aptamer Against Hccmentioning

confidence: 99%

Aptamer: A potential oligonucleotide nanomedicine in the diagnosis and treatment of hepatocellular carcinoma

et al. 2017

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“…The approaches taken could be extended to other cell surface markers by developing specific apt and used in combination with EpCAM to improve targeting to cancer cells. Likewise, other types of EpCAM‐targeting apt nanoparticles could be developed for gene targeting or drug delivery into cancer cells …”

Section: Discussionmentioning

confidence: 99%

Targeting Liver Cancer Stem Cells Using Engineered Biological Nanoparticles for the Treatment of Hepatocellular Cancer

Ishiguro¹,

Yan²,

Lewis‐Tuffin³

et al. 2020

Hepatol Commun

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By exploiting their biological functions, the use of biological nanoparticles such as extracellular vesicles can provide an efficient and effective approach for hepatic delivery of RNA-based therapeutics for the treatment of liver cancers such as hepatocellular cancer (HCC). Targeting liver cancer stem cells (LCSC) within HCC provide an untapped opportunity to improve outcomes by enhancing therapeutic responses. Cells with tumor-initiating capabilities such as LCSC can be identified by expression of markers such as epithelial cell adhesion molecule (EpCAM) on their cell surface. EpCAM is a target of Wnt/β-catenin signaling, a fundamental pathway in stem-cell growth. Moreover, mutations in the β-catenin gene are frequently observed in HCC and can be associated with constitutive activation of the Wnt/β-catenin pathway. However, targeting these pathways for the treatment of HCC has been challenging. Using RNA nanotechnology, we developed engineered biological nanoparticles capable of specific and effective delivery of RNA therapeutics targeting β-catenin to LCSC. Extracellular vesicles isolated from milk were loaded with small interfering RNA to β-catenin and decorated with RNA scaffolds to incorporate RNA aptamers capable of binding to EpCAM. Cellular uptake of these EpCAM-targeting therapeutic milk-derived nanovesicles in vitro resulted in loss of β-catenin expression and decreased proliferation. The uptake and therapeutic efficacy of these engineered biological nanotherapeutics was demonstrated in vivo using tumor xenograft mouse models. Conclusion: β-catenin can be targeted directly to control the proliferation of hepatic cancer stem cells using small interfering RNA delivered using target-specific biological nanoparticles. Application of this RNA nanotechnology-based approach to engineer biological nanotherapeutics provides a platform for developing cell-surface molecule-directed targeted therapeutics. (Hepatology Communications 2020;4:298-313).

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“…Tumor volume was measured using calipers, and after tumor volumes reached approximately 350 mm 3 , all test candidates were divided into four groups, including normal saline group, naked VEGF-siRNA (0.3 mg/kg) group, GRcR/ VEGF-siRNA (0.3 mg/kg) group, and DOX (2 µmol/kg) group randomly (10 animals each). The test candidates and controls were given to all mice intravenously five times every other day [ 44 , 45 ]. All mice were sacrificed after the last injection, tumors, organs, and blood were harvested and stored for further use.…”

Section: Methodsmentioning

confidence: 99%

Preparation and Characterization of Functionalized Graphene Oxide Carrier for siRNA Delivery

Cui

et al. 2018

IJMS

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A successful siRNA delivery system is dependent on the development of a good siRNA carrier. Graphene oxide (GO) has gained great attention as a promising nanocarrier in recent years. It has been reported that GO could be used to deliver a series of drugs including synthetic compounds, proteins, antibodies, and genes. Our previous research indicated that functionalized GO could deliver siRNA into tumor cells and induce a gene silencing effect, to follow up the research, in this research, GO-R8/cRGDfV(GRcR) was designed and prepared for VEGF-siRNA delivery as a novel carrier. The Zeta potential and particle size of the new designed GRcR carrier was measured at (29.46 ± 5.32) mV and (135.7 ± 3.3) nm respectively, and after transfection, the VEGF mRNA level and protein expression level were down-regulated by 48.22% (p < 0.01) and 38.3% (p < 0.01) in HeLa cells, respectively. The fluorescent images of the treated BALB/c nude mice revealed that GRcR/VEGF-siRNA could conduct targeted delivery of VEGF-siRNA into tumor tissues and showed a gene silencing effect as well as a tumor growth inhibitory effect (p < 0.01) in vivo. Further studies showed that GRcR/VEGF-siRNA could effectively inhibit angiogenesis by suppressing VEGF expression. Histology and immunohistochemistry studies demonstrated that GRcR/VEGF-siRNA could inhibit tumor tissue growth effectively and have anti-angiogenesis activity, which was the result of VEGF protein downregulation. Both in vitro and in vivo results demonstrated that GRcR/VEGF-siRNA could be used as an ideal nonviral tumor-targeting vector for VEGF-siRNA delivery in gene therapy.

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Aptamer-mediated gene therapy enhanced antitumor activity against human hepatocellular carcinoma in vitro and in vivo

Cited by 27 publications

References 33 publications

Aptamer: A potential oligonucleotide nanomedicine in the diagnosis and treatment of hepatocellular carcinoma

Aptamer: A potential oligonucleotide nanomedicine in the diagnosis and treatment of hepatocellular carcinoma

Targeting Liver Cancer Stem Cells Using Engineered Biological Nanoparticles for the Treatment of Hepatocellular Cancer

Preparation and Characterization of Functionalized Graphene Oxide Carrier for siRNA Delivery

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