Functionalized nanogels carrying an anticancer microRNA for glioblastoma therapy

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	Functionalized nanogels carrying an anticancer microRNA for glioblastoma therapy
	Shatsberg, Zohar 1; Zhang, Xuejiao 2,3; Ofek, Paula 1; Malhotra, Shashwat 2; Krivitsky, Adva 1; Scomparin, Anna 1; Tiram, Galia 1; Calderon, Marcelo 2; Haag, Rainer 2; Satchi-Fainaro, Ronit 1
刊名	JOURNAL OF CONTROLLED RELEASE
	2016-10-10
卷号	239 页码:159-168
关键词	Polymer therapeutics Nanogels Polyplex Polycations Polyglycerol microRNAs miR-34a Glioblastoma Nanomedicine
英文摘要	Glioblastoma Multiforme (GBM) is one of the most aggressive forms of all cancers. The median survival with current standard-of-care radiation and chemotherapy is about 14 months. GBM is difficult to treat due to heterogeneity in cancer cell population. MicroRNA-based drugs have rapidly become a vast and burgeoning field due to the ability of a microRNA (miRNA) to target many genes involved in key cellular pathways. However, in vivo delivery of miRNA remains a crucial challenge for its therapeutic success. To bypass this shortcoming, we designed polymeric nanogels (NGs), which are based on a polyglycerol-scaffold, as a new strategy of miRNA delivery for GBM therapy. We focused on miR-34a, which is known for its key role in important oncogenic pathways and its tumor suppression ability in GBM and other cancers. We evaluated the capability of six NG derivatives to complex with miR-34a, neutralize its negative charge and deliver active miRNA to the cell cytoplasm. Human U-87 MG GBM cells treated with our NG-miR-34a nano-polyplexes showed remarkable downregulation of miR-34a target genes, which play key roles in the regulation of apoptosis and cell cycle arrest, and induce inhibition of cells proliferation and migration. Administration of NG-miR-34a nano-polyplexes to human U-87MG GBM-bearing SCID mice significantly inhibited tumor growth as opposed to treatment with NG-negative control miR polyplex or saline. The comparison between different polyplexes highlighted the key features for the rational design of polymeric delivery systems for oligonucleotides. Taken together, we expect that this new therapeutic approach will pave the way for safe and efficient therapies for GBM. (C) 2016 Elsevier B.V. All rights reserved.
WOS标题词	Science & Technology ; Physical Sciences ; Life Sciences & Biomedicine
类目[WOS]	Chemistry, Multidisciplinary ; Pharmacology & Pharmacy
研究领域[WOS]	Chemistry ; Pharmacology & Pharmacy
关键词[WOS]	HEPATOCELLULAR-CARCINOMA CELLS ; TARGETED SIRNA DELIVERY ; NONVIRAL GENE DELIVERY ; CANCER STEM-CELLS ; IN-VIVO DELIVERY ; DOWN-REGULATION ; BIOMEDICAL APPLICATIONS ; POLYMER THERAPEUTICS ; REPLACEMENT THERAPY ; CELLULAR UPTAKE
收录类别	SCI
语种	英语
WOS记录号	WOS:000384700200016
内容类型	期刊论文
源URL	[http://210.72.129.5/handle/321005/65921]
专题	沈阳应用生态研究所_沈阳应用生态研究所_期刊论文
作者单位	1.Tel Aviv Univ, Sackler Sch Med, Dept Physiol & Pharmacol, IL-69978 Tel Aviv, Israel 2.Free Univ Berlin, Inst Chem & Biochem, Takustr 3, D-14195 Berlin, Germany 3.Chinese Acad Sci, Inst Appl Ecol, Key Lab Pollut Ecol & Environm Engn, Shenyang 110016, Peoples R China
推荐引用方式 GB/T 7714	Shatsberg, Zohar,Zhang, Xuejiao,Ofek, Paula,et al. Functionalized nanogels carrying an anticancer microRNA for glioblastoma therapy[J]. JOURNAL OF CONTROLLED RELEASE,2016,239:159-168.
APA	Shatsberg, Zohar.,Zhang, Xuejiao.,Ofek, Paula.,Malhotra, Shashwat.,Krivitsky, Adva.,...&Satchi-Fainaro, Ronit.(2016).Functionalized nanogels carrying an anticancer microRNA for glioblastoma therapy.JOURNAL OF CONTROLLED RELEASE,239,159-168.
MLA	Shatsberg, Zohar,et al."Functionalized nanogels carrying an anticancer microRNA for glioblastoma therapy".JOURNAL OF CONTROLLED RELEASE 239(2016):159-168.