Improvement of gene delivery mediated by mannosylated dendrimer/α-cyclodextrin conjugates

Wada, Koh; Arima, Hisatomi; Tsutsumi, Toshihito; Chihara, Yuko; Hattori, Kiyohiko; Hirayama, Fumitoshi; Uekama, Kaneto

doi:10.1016/j.jconrel.2005.02.016

Cited by 130 publications

(85 citation statements)

References 47 publications

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“…Mannose receptor expression in the kidney is restricted to the mesangium [19,20] and has been demonstrated to facilitate uptake of nanoparticles by macrophages in vivo [25,26]. The transferrin receptor, although up-regulated within the mesangium of patients with IgA nephropathy [27][28][29], is not highly expressed in the healthy glomerulus, but has been demonstrated to facilitate intracellular uptake of the transferrin-targeted siRNA/CDP-NPs in other cell lines [17,21].…”

Section: Discussionmentioning

confidence: 99%

siRNA Delivery to the Glomerular Mesangium Using Polycationic Cyclodextrin Nanoparticles Containing siRNA

Zuckerman

Gale

et al. 2015

Nucleic Acid Therapeutics

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There is an urgent need for new therapies that can halt or reverse the course of chronic kidney disease with minimal side-effect burden on the patient. Small interfering RNA (siRNA) nanoparticles are new therapeutic entities in clinical development that could be useful for chronic kidney disease treatment because they combine the tissuespecific targeting properties of nanoparticles with the gene-specific silencing effects of siRNA. Recent reports have emerged demonstrating that the kidney, specifically the glomerulus, is a readily accessible site for nanoparticle targeting. Here, we explore the hypothesis that intravenously administered polycationic cyclodextrin nanoparticles containing siRNA (siRNA/CDP-NPs) can be used for delivery of siRNA to the glomerular mesangium. We demonstrate that siRNA/CDP-NPs localize to the glomerular mesangium with limited deposition in other areas of the kidney after intravenous injection. Additionally, we report that both mouse and human mesangial cells rapidly internalize siRNA/CDP-NPs in vitro and that nanoparticle uptake can be enhanced by attaching the targeting ligands mannose or transferrin to the nanoparticle surface. Lastly, we show knockdown of mesangial enhanced green fluorescent protein expression in a reporter mouse strain following iv treatment with siRNA/CDP-NPs. Altogether, these data demonstrate the feasibility of mesangial targeting using intravenously administered siRNA/CDP-NPs.

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Section: Discussionmentioning

confidence: 99%

siRNA Delivery to the Glomerular Mesangium Using Polycationic Cyclodextrin Nanoparticles Containing siRNA

Zuckerman

Gale

et al. 2015

Nucleic Acid Therapeutics

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“…It was found to stabilize the polyplex nanoparticles and results in enhanced gene transfection [108,109]. So far, a number of cationic polymers have been modified by grafting CDs onto the polymers to study gene delivery, such as linear and branched PEIs [110], and polyamidoamine (PAMAM) dentrimers [111,112]. All the CD-grafted cationic polymers showed reduced cytotoxicity by grafting the CD moieties.…”

Section: Cyclodextrin-containing Cationic Polymers For Gene Deliverymentioning

confidence: 99%

“…All the CD-grafted cationic polymers showed reduced cytotoxicity by grafting the CD moieties. Uekama et al [111][112][113][114][115][116] systematically studied CD-grafting PAMAM dendrimers with different generations (G2, G3, and G4) and attributed the enhancing gene transfection effect to increasing cellular association and intracellular trafficking of plasmid DNA.…”

Section: Cyclodextrin-containing Cationic Polymers For Gene Deliverymentioning

confidence: 99%

Supramolecular Polymers Based on Cyclodextrins for Drug and Gene Delivery

Zhao

2010

Biofunctionalization of Polymers and Their Applications

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Supramolecular polymers based on cyclodextrins (CDs) have inspired interesting and rapid developments as novel biomaterials in a broad range of drug and gene delivery applications, due to their low cytotoxicity, controllable size, and unique architecture. This review will summarize the potential applications of polyrotaxanes in the field of drug delivery and gene delivery. Generally, cyclodextrin-based biodegradable polypseudorotaxane hydrogels could be used as a promising injectable drug delivery system for sustained and controlled drug release. Temperature-responsive, pH-sensitive, and controllable hydrolyzable polyrotaxane hydrogels have attracted much attention because of their controllable properties, and the self-assembly micelles formed by amphiphilic copolymer threaded with CDs could be used as a carrier for controlled and sustained drug release. Polyrotaxanes with drug or ligand conjugated CDs threaded on a polymer chain with a biodegradable end group could be useful for controlled and multivalent targeted delivery. In the field of gene delivery, cationic polyrotaxanes consisting of multiple OEI-grafted CDs threaded on a block copolymer chain are attractive non-viral gene carries due to the strong DNA-binding ability, low cytotoxicity, and high gene delivery capability. Furthermore, cytocleavable end-caps were introduced in the polyrotaxane systems in order to ensure efficient endosomal escape for intracellular trafficking of DNA. The development of the supramolecular approach using CD-containing polyrotaxanes is expected to provide a new paradigm for biomaterials.

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“…However, their transduction efficiency is very low. Efforts have recently been directed towards improving this aspect (Mizuguchi et al 1996;Kogure et al 2004;Wada et al 2005). In 1987, Fechherimer et al (1987 reported a new concept about application of ultrasound energy for gene delivery.…”

Section: Introductionmentioning

confidence: 99%

Effective gene delivery with liposomal bubbles and ultrasound as novel non-viral system

Suzuki

Takizawa

Negishi

et al. 2007

Journal of Drug Targeting

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We developed the novel liposomal bubbles (Bubble liposomes) containing ultrasound imaging gas, perfluoropropane. Bubble liposomes were made of pegylated liposomes and were smaller than conventional microbubbles. Bubble liposomes also had a function as imaging agents in cardiosonography. In addition, Bubble liposomes could deliver plasmid DNA into various types of cells in vitro without cytotoxicity by the combination of ultrasound. In vivo gene delivery, Bubble liposomes could deliver plasmid DNA into mouse femoral artery by the transdermally exposure of ultrasound. This transfection efficiency was more effectively than lipofection method. Interestingly, the gene expression was only observed at the site of ultrasound exposure. Therefore, we concluded that Bubble liposomes could be good tools to establish tissue-specific gene delivery system as well as ultrasound imaging agents.

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Improvement of gene delivery mediated by mannosylated dendrimer/α-cyclodextrin conjugates

Cited by 130 publications

References 47 publications

siRNA Delivery to the Glomerular Mesangium Using Polycationic Cyclodextrin Nanoparticles Containing siRNA

siRNA Delivery to the Glomerular Mesangium Using Polycationic Cyclodextrin Nanoparticles Containing siRNA

Supramolecular Polymers Based on Cyclodextrins for Drug and Gene Delivery

Effective gene delivery with liposomal bubbles and ultrasound as novel non-viral system

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