Cationic microRNA-delivering nanovectors with bifunctional peptides for efficient treatment of PANC-1 xenograft model

Hu, Qiang; Jiang, Qiong; Jin, Xiaodong; Shen, Jingnan; Wang, K.; Li, Y.B.; Xu, Fu‐Jian; Tang, Guping; Li, Z.H.

doi:10.1016/j.biomaterials.2012.12.016

Cited by 100 publications

(81 citation statements)

References 30 publications

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“…It has been demonstrated that miR-34a regulates apoptosis by targeting Bcl-2 in various tumor cells (Cole et al, 2008;Hu et al, 2013;Ji et al, 2012;Kastl et al, 2012;Liu et al, 2011;Liu, 2010;Mraz et al, 2009;Nalls et al, 2011;Peng et al, 2013;Yang et al, 2013). Here, in cultured proximal tubular cells, the upregulation of miR-34a by microvesicle delivery or mimic transfection induced cell apoptosis, whereas downregulation of miR-34a by inhibitor transfection inhibited apoptosis (Figs 3, 4).…”

Section: Discussionmentioning

confidence: 79%

Secreted fibroblast miR-34a induces tubular cell apoptosis in fibrotic kidney

Zhou

Xiong

Niu

et al. 2014

Journal of Cell Science

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Tubular epithelial cell apoptosis contributes to tubulointerstitial fibrosis but its regulation remained unclear. Here, in fibrotic kidney induced by unilateral ureteral obstruction (UUO), we demonstrated that miR-34a was markedly up-regulated in tubulointerstitial spaces and microvesicles isolated from kidney. However, the increased miR-34a was not de novo synthesized by proximal tubular epithelial cells but by fibroblasts after incubated with TGF-β1. MiR-34a was markedly up-regulated in microvesicles isolated from cell culture media of TGF-β1 treated fibroblasts. These microvesicles acted as a vector for delivery of up-regulated miR-34a from fibroblasts to tubular cells. The fibroblast-derived miR-34a-containing microvesicles induced apoptosis of tubular cells. The exogenous miR-34a regulated tubular apoptosis by modulating the expression of anti-apoptotic protein Bcl-2. Moreover, injection of exogenous miR-34a-containing microvesicles enhanced tubular cell apoptosis in mice. This study suggests that secreted fibroblast miR-34a transported by microvesicles induces tubular cell apoptosis in obstructive kidney. This study provided a new mechanism concerning microvesicle-mediated fibroblast-to-tubular cell communication of miRNA in regulating tubular cell apoptosis, which might provide new therapeutic targets for renal tubulointerstitial fibrosis.

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Section: Discussionmentioning

confidence: 79%

Secreted fibroblast miR-34a induces tubular cell apoptosis in fibrotic kidney

Zhou

Xiong

Niu

et al. 2014

Journal of Cell Science

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“…Hu et al synthesized polyethylenimine-β-cyclodextrin (PEI-CD) by crosslinking β-CD with low molecular weight PEI (600 Da), and conjugated a tumor homing and penetrating bifunctional peptide CC9 (CRGDKGPDC). Formulation complexed with miR-34a was able to accumulate significantly at the tumor site and downregulated target genes, such as E2F3, Bcl-2, c-myc and cyclin D1 (150).…”

Section: Targeted Particulate Systemsmentioning

confidence: 99%

Delivery and Targeting of miRNAs for Treating Liver Fibrosis

Kumar

Mahato

2014

Pharm Res

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Liver fibrosis is a pathological condition originating from liver damage that leads to excess accumulation of extracellular matrix (ECM) proteins in the liver. Viral infection, chronic injury, local inflammatory responses and oxidative stress are the major factors contributing to the onset and progression of liver fibrosis. Multiple cell types and various growth factors and inflammatory cytokines are involved in the induction and progression of this disease. Various strategies currently being tried to attenuate liver fibrosis include the inhibition of HSC activation or induction of their apoptosis, reduction of collagen production and deposition, decrease in inflammation, and liver transplantation. Liver fibrosis treatment approaches are mainly based on small drug molecules, antibodies, oligonucleotides (ODNs), siRNA and miRNAs. MicroRNAs (miRNA or miR) are endogenous noncoding RNA of ~22 nucleotides that regulate gene expression at post transcription level. There are several miRNAs having aberrant expressions and play a key role in the pathogenesis of liver fibrosis. Single miRNA can target multiple mRNAs, and we can predict its targets based on seed region pairing, thermodynamic stability of pairing and species conservation. For in vivo delivery, we need some additional chemical modification in their structure, and suitable delivery systems like micelles, liposomes and conjugation with targeting or stabilizing the moiety. Here, we discuss the role of miRNAs in fibrogenesis and current approaches of utilizing these miRNAs for treating liver fibrosis.

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“…[ 15 ] Therefore, more and more researchers have been focusing on nonviral vectors for miRNAs delivery. [ 16 ] Compared with those commonly used nonviral vectors, such as lipid-based nanocarriers, polymeric vectors, and amphiphilic star-branched copolymers, [17][18][19] gold nanocages (AuNCs) have received more attention as one of the nonviral gene delivery vectors due to their unique physicochemical properties and easy surface functionalized modifi cation. [ 20 ] As illustrated in previous studies, gold nanocages have the strong optical absorption in the near-infrared region (NIR, 700-1100 nm).…”

Section: Folic-acid-mediated Functionalized Gold Nanocages For Targetmentioning

confidence: 99%

Folic‐Acid‐Mediated Functionalized Gold Nanocages for Targeted Delivery of Anti‐miR‐181b in Combination of Gene Therapy and Photothermal Therapy against Hepatocellular Carcinoma

Huang

Duan

Wang

et al. 2016

Adv Funct Materials

117

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Therapeutic strategies based on modulation of microRNAs (miRNAs) activity hold much promise for cancer therapy, but for clinical applications, the effi cient delivery of miRNAs to tumor cells or tumor tissues remains a great challenge. In this work, microRNA-181b inhibitor (anti-miR-181b) is successfully condensed into polyethyleneimine (PEI)-modifi ed and folate receptor (FR)-targeted PEGylated gold nanocages (AuNCs). This delivery system is designated as anti-miR-181b/PTPAuNCs nanocomplexes (PTPAuNC-NPs), which begin with chemical modifi cation of AuNCs with SH-PEG 5000 -folic acid (SH-PEG 5000 -FA) and SH-PEG 5000 through a gold-sulfur bond, followed by conjugating PEI using lipoic acid as a linker. Finally anti-miR-181b is condensed via electrostatic interactions. In vitro and in vivo experiments show that PTPAuNC-NPs can effi ciently deliver anti-miR-181b into target sites to suppress tumor growth, and considerably decrease tumor volumes in SMMC-7721 tumor-bearing nude mice under near-infrared radiation. All these results suggest that PTPAuNC-NP gene delivery system with combination of gene therapy and photothermal therapy will be of great potential use in future cancer therapy.

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Cationic microRNA-delivering nanovectors with bifunctional peptides for efficient treatment of PANC-1 xenograft model

Cited by 100 publications

References 30 publications

Secreted fibroblast miR-34a induces tubular cell apoptosis in fibrotic kidney

Secreted fibroblast miR-34a induces tubular cell apoptosis in fibrotic kidney

Delivery and Targeting of miRNAs for Treating Liver Fibrosis

Folic‐Acid‐Mediated Functionalized Gold Nanocages for Targeted Delivery of Anti‐miR‐181b in Combination of Gene Therapy and Photothermal Therapy against Hepatocellular Carcinoma

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