Efficient delivery of siRNA using dendritic poly(l-lysine) for loss-of-function analysis

Inoue, Yusuke; Kurihara, Ryosuke; Tsuchida, Akiko; Hasegawa, Mino; Nagashima, Takahiro; Mori, Takeshi; Niidome, Takuro; Katayama, Yoshiki; Okitsu, Osamu

doi:10.1016/j.jconrel.2007.10.022

Cited by 105 publications

(70 citation statements)

References 35 publications

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“…2). This indicates that our SNPs deliver more siRNA than many delivery vehicles (using LF2K delivery as a reference) 53–55 . However, the degree of silencing achieved by the delivered siRNAs was only comparable to LF2K.…”

Section: Discussionmentioning

confidence: 89%

Dextran functionalization enhances nanoparticle-mediated siRNA delivery and silencing

et al. 2016

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Understanding the endocytosis and intracellular trafficking of short interfering RNA (siRNA) delivery vehicle complexes remains a critical bottleneck in designing siRNA delivery vehicles for highly active RNA interference (RNAi)-based therapeutics. In this study, we show that dextran functionalization of silica nanoparticles enhanced uptake and intracellular delivery of siRNAs in cultured cells. Using pharmacological inhibitors for endocytotic pathways, we determined that our complexes are endocytosed via a previously unreported mechanism for siRNA delivery in which dextran initiates scavenger receptor-mediated endocytosis through a clathrin/caveolin-independent process. Our findings suggest that siRNA delivery efficiency could be enhanced by incorporating dextran into existing delivery platforms to activate scavenger receptor activity across a variety of target cell types.

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Section: Discussionmentioning

confidence: 89%

Dextran functionalization enhances nanoparticle-mediated siRNA delivery and silencing

et al. 2016

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“…Among the polymers commonly employed as non-viral si-RNA delivery systems, chitosan (Ma et al, 2014;Ozpolat et al, 2014;Xie et al, 2014), poly(ethylene imine) (Urban-Klein et al, 2005;Nabzdyk et al, 2014), poly(amidoamine) dendrimers (Patil et al, 2008;Conti et al, 2014) and poly(L-lysine) (Inoue et al, 2008;Kodama et al, 2014) have been extensively investigated.…”

Section: Introductionmentioning

confidence: 99%

EpCAM-targeted liposomal si-RNA delivery for treatment of epithelial cancer

et al. 2014

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Background: RNA interference (RNAi) technology using short interfering RNA (si-RNA) has shown immense potential in the treatment of cancers through silencing of specific genes. Cationic non-viral vectors employed for gene delivery exhibit toxic effects in normal cells limiting their widespread use, therefore, site-specific delivery using benign carriers could address this issue. Objective: Design of a non-toxic carrier that enables site-specific delivery of si-RNA into the cancer cells is of prime importance to realize the promise of gene silencing. Methods: In the present study, non-cationic liposomes encapsulating si-RNA against epithelial cell adhesion molecule (EpCAM) were developed and characterized for encapsulation efficiency, colloidal stability, in vitro and in vivo gene silencing efficacy. Results: PEGylated liposomes containing phosphatidyl choline and phosphatidyl ethanolamine exhibited maximum si-RNA encapsulation efficiency of 47%, zeta potential of -21 mV, phase transition temperature of 51 C and good colloidal stability in phosphate-buffered saline (PBS) containing bovine serum albumin (BSA) and plasma protein (PP) at 37 C. Conjugation of epithelial cell adhesion molecule (EpCAM) antibody to the liposomes resulted in enhanced cell internalization and superior down-regulation of EpCAM gene in MCF-7 cell lines when compared with free si-RNA and the non-targeted liposomes. In vivo evaluation of immunoliposomes for their efficacy in regressing the tumor volume in Balb/c SCID mice showed about 35% reduction of tumor volume in comparison with the positive control when administered with an extremely low dose of 0.15 mg/kg twice a week for 4 weeks. Conclusion: Our results exhibit that the nanocarrier-mediated silencing of EpCAM gene is a promising strategy to treat epithelial cancers.

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“…They are now commercially available and were also studied for siRNA delivery. Inoue et al recommended the use of polylysine dendrimers for siRNA transfer and found that dendriplexes based on polylysine dendrimers and siRNA reveal low toxicity and cause proficient knockdown of the glyceraldehydes-3 phosphate dehydrogenase gene in several cell lines [93].…”

Section: Purpose Of Investigationmentioning

confidence: 99%