A biomimetic nanovector-mediated targeted cholesterol-conjugated siRNA delivery for tumor gene therapy

Ding, Yang; Wang, Wei; Feng, Meiqing; Wang, Yu; Zhou, Jianping; Ding, Xuefang; Zhou, Xin; Liu, Congyan; Wang, Ruoning; Zhang, Qiang

doi:10.1016/j.biomaterials.2012.08.057

Cited by 116 publications

(95 citation statements)

References 42 publications

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“…Intriguingly, nanovector-mediated Pokemon silencing was demonstrated to decrease the survival and proliferation of HCC cell lines [7]. However, the association between Pokemon expression and HCC invasion has not been established yet.…”

Section: Introductionmentioning

confidence: 98%

Pokemon and MEF2D co-operationally promote invasion of hepatocellular carcinoma

Hong

et al. 2015

Tumor Biol.

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Hepatocellular carcinoma (HCC) is one of the most deadly human malignancy, and frequent invasion and metastasis is closely associated with its poor prognosis. However, the molecular mechanism underlying HCC invasion is still not completely elucidated. Pokemon is a well-established oncogene for HCC growth, but its contribution to HCC invasion has not been studied yet. In this paper, Pokemon was found to be overexpressed in MHCC-97H HCC cell line, which possesses higher invasiveness. Downregulation of Pokemon abolished the invasion of MHCC-97H HCC cell lines. Pokemon overexpression was able to enhance the invasion of MHCC-97L cells with lower invasiveness. MEF2D, an oncogene promoting the invasion of HCC cells, was further detected to be upregulated and downregulated when Pokemon was overexpressed and silenced, respectively. Online database analysis indicated that one Pokemon recognition site was located within the promoter of MEF2D. Chromatin co-precipitation, luciferase, and qPCR assays all proved that Pokemon can promote the expression of MEF2D in HCC cells. Restoration of MEF2D expression can prevent the impaired invasion of HCC cells with Pokemon silencing, while suppression of MEF2D abolished the effect of Pokemon overexpression on HCC invasion. More interestingly, MEF2D was also found to increase the transcription of Pokemon by binding myocyte enhancer factor 2 (MEF2) sites within its promoter region, implying an auto-regulatory circuit consisting of these two oncogenes that can promote HCC invasion. Our findings can contribute to the understanding of molecular mechanism underlying HCC invasion, and provided evidence that targeting this molecular loop may be a promising strategy for anti-invasion therapy.

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Section: Introductionmentioning

confidence: 98%

Pokemon and MEF2D co-operationally promote invasion of hepatocellular carcinoma

Hong

et al. 2015

Tumor Biol.

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“…233 The SR-B1 is broadly overexpressed among various cancer cells including HCC and SR-B1 receptor-mediated HDL uptake makes HDL a promising target delivery vehicle for therapeutics. 234 The rHDL was utilized as a biomimetic nanovector by Ding et al, 235 mediating HCC-targeted cholesterol-conjugated siRNA (Chol-siRNA) delivery. rHDL could enhance cellular uptake and in vitro cytotoxicity of the siRNA and specifically target it into cytoplasm.…”

mentioning

confidence: 99%

Ligand-based targeted therapy: a novel strategy for hepatocellular carcinoma

Li¹,

Zhang²,

Wang³

et al. 2016

IJN

117

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“…Human breast cancer cell line (MCF-7) was selected for cytotoxicity and phagocytosis studies because cellular uptake of PTX from d-rHDL is facilitated by SR-BI which was overexpressed on MCF-7 (Ding et al, 2012;Sabnis & Lacko, 2012). cP-d-rHDL possessed higher toxic actions than P-drHDL, and cytotoxicity of the former was not affected by LCAT.…”

Section: Discussionmentioning

confidence: 99%

Tumor targeting effects of a novel modified paclitaxel-loaded discoidal mimic high density lipoproteins

et al. 2013

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Objective: Monocholesterylsuccinate (CHS)-modified paclitaxel-loaded discoidal reconstituted high density lipoproteins (cP-d-rHDL) as novel biomimetic nanocarriers that were developed for tumor targeting delivery to avoid unexpected drug leakage from discoidal reconstituted high density lipoproteins (d-rHDL) during remodeling process associated with lecithin-cholesterol acyltransferase (LCAT). Methods: Their in vitro characterizations and biomimetic properties, simultaneously tumor distribution and pharmacodynamics in tumor bearing mice were elaborately investigated. Results: In vitro characterization results showed that cP-d-rHDL had nano-size diameter, high negative zeta potential and high entrapment efficiency (EE). Furthermore, morphology study indicated that cP-d-rHDL did not remodel in the presence of LCAT, compared with that of paclitaxel-loaded d-rHDL (P-d-rHDL, not modified). And cellular uptake, together with cytotoxicity toward tumor cells of cP-d-rHDL was not affected after interaction with LCAT. Tumor distribution and pharmacodynamics tests revealed that cP-d-rHDL possessed specific targeting property and anti-tumor efficacy. Conclusion: cP-d-rHDL served to restrain remodeling process and drug leakage, at the same time reinforce the targeting effect, and could act as a potential drug delivery system for cancer therapy.

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A biomimetic nanovector-mediated targeted cholesterol-conjugated siRNA delivery for tumor gene therapy

Cited by 116 publications

References 42 publications

Pokemon and MEF2D co-operationally promote invasion of hepatocellular carcinoma

Pokemon and MEF2D co-operationally promote invasion of hepatocellular carcinoma

Ligand-based targeted therapy: a novel strategy for hepatocellular carcinoma

Tumor targeting effects of a novel modified paclitaxel-loaded discoidal mimic high density lipoproteins

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