Cellular internalization and gene silencing of siRNA polyplexes by cytocleavable cationic polyrotaxanes with tailored rigid backbones

Tamura, Atsushi; Yui, Nobuhiko

doi:10.1016/j.biomaterials.2012.12.006

Cited by 60 publications

(67 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In previous studies our group has demonstrated the potential of linear and branched cationic α-CD PR + as efficient siRNA delivery vehicles [21, 22]. Recently Yui group has developed the PEG based PR + with α-CDs for siRNA delivery and shown that more highly threaded PR + are more effective siRNA delivery agents [23]. By varying the number of threading CDs and Dimethylethanolamine (DMAE) groups on the PR, they established a relationship between charge density and threading efficiency on the performance of DMAE-PR + /siRNA polyplexes.…”

Section: Introductionmentioning

confidence: 99%

Structure-property relationship for in vitro siRNA delivery performance of cationic 2-hydroxypropyl-β-cyclodextrin: PEG-PPG-PEG polyrotaxane vectors

et al. 2016

View full text Add to dashboard Cite

Nanoparticle-mediated siRNA delivery is a promising therapeutic approach, however, yet the processes required for transport of these materials across the numerous extracellular and intracellular barriers are poorly understood. Efficient delivery of siRNA-containing nanoparticles would ultimately benefit from an improved understanding of how parameters associated with these barriers relate to the physicochemical properties of the nanoparticle vectors. We report the synthesis of three Pluronic®-based, cholesterol end-capped cationic polyrotaxanes (PR+) threaded with 2-hydroxypropyl-β-cyclodextrin (HPβCD) for siRNA delivery. The biological data showed that PR+:siRNA complexes were well tolerated (~90% cell viability) and produced efficient silencing (>80%) in HeLa-GFP and NIH 3T3-GFP cell lines. We further used a multi-parametric approach to identify relationships between the PR+ structure, PR+:siRNA complex physical properties, and biological activity. Small angle x-ray scattering and cryoelectron microscopy studies reveal periodicity and lamellar architectures for PR+:siRNA complexes, whereas the biological assays, ζ potential measurements, and imaging studies suggest that silencing efficiency is influenced by the effective charge ratio (ρeff), polypropylene oxide (PO) block length, and central PO block coverage (i.e., rigidity) of the PR+ core. We infer from our findings that more compact PR+:siRNA nanostructures arising from lower molecular weight, rigid rod-like PR+ polymer cores produce improved silencing efficiency relative to higher molecular weight, more flexible PR+ vectors of similar effective charge. This study demonstrates that PR+:siRNA complex formulations can be produced having higher performance than Lipofectamine® 2000, while maintaining good cell viability and siRNA sequence protection in cell culture.

show abstract

Section: Introductionmentioning

confidence: 99%

Structure-property relationship for in vitro siRNA delivery performance of cationic 2-hydroxypropyl-β-cyclodextrin: PEG-PPG-PEG polyrotaxane vectors

et al. 2016

View full text Add to dashboard Cite

show abstract

“…In some cases, an increase in the number of threading CDs in PRXs is a predominant factor to enhance the physicochemical stability of polyelectrolyte complexes with nucleic acids and their intracellular uptake efficiency. 5 These results indicate the importance of the conformation of PRXs chains.…”

Section: Introductionmentioning

confidence: 94%

“…Yui and colleagues 4,5 have studied the biomaterial application of PRXs such as a delivery carrier for genes or proteins using their unique supramolecular functions, which include the stimuli-induced dissociation through the cleavage of terminal bulky stoppers and the freely mobile nature of threading CDs along the polymer chain. In some cases, an increase in the number of threading CDs in PRXs is a predominant factor to enhance the physicochemical stability of polyelectrolyte complexes with nucleic acids and their intracellular uptake efficiency.…”

Section: Introductionmentioning

confidence: 99%

Chain architecture and flexibility of α-cyclodextrin/PEG polyrotaxanes in dilute solutions

Yamada

Sanada

Tamura

et al. 2015

Polym J

Self Cite

View full text Add to dashboard Cite

“…In vitro [106] Chitosan-graft-(PEI-b-CyD) copolymers b-CyD Luciferase In vitro [110] Cationic a-CyD: PEG polyrotaxane a-CyD Luciferase In vitro [107] Multi-armed cationic CyD: PEG polyrotaxane a-CyD GFP In vitro [108] Cytocleavable cationic polyrotaxane a-CyD Luciferase In vitro [112] PEI crosslinked HP-b-CyD and folic acid HP-b-CyD VEGF i.v. [109] Quantum-dot nanoparticles coated with b-CyD b-CyD HPV18 E6 gene In vitro [114] CyD-modified dendritic polyamine b-CyD EGFR In vitro [105] CyD/dendrimer conjugate a-CyD Luciferase, Fas, cells [143,144].…”

Section: Sugar-appended A-cde As Kupffer Cell-selective Gene and Oligmentioning

confidence: 99%

“…So far, CyD polymer, CyD polyrotaxane and CyD/dendrimer conjugate have been developed as gene and siRNA carriers. Table 1 summarizes CyD-based non-viral vectors for siRNA [24,25,[98][99][100][101][102][103][104][105][106][107][108][109][110][111][112][113][114]. In addition, amphiphilic CyDs are also utilized not only as low-molecular-weight drug carriers or gene transfer carriers but also as siRNA carriers [115][116][117][118][119][120][121].…”

Section: Other Cyd-based Drug Carriers For Peptides and Proteinsmentioning

confidence: 99%

Recent advances in cyclodextrin delivery techniques

Arima

Hayashi

Higashi

et al. 2015

Expert Opinion on Drug Delivery

View full text Add to dashboard Cite

To achieve the controlled release and/or targeting of low-molecular-weight drugs in systemic administration, the construction of novel CyDs and CyD the supramolecular system should be a useful approach because of the stable complexation of drugs with CyDs. In addition, the combination systems of CyDs and various carriers have the potential as advanced drug delivery systems for proteins and nucleic acids. Furthermore, CyDs have great potential as APIs for various diseases with few side effects, although the detailed mechanism, especially cellular uptake of CyDs, should be clarified.

show abstract

Cellular internalization and gene silencing of siRNA polyplexes by cytocleavable cationic polyrotaxanes with tailored rigid backbones

Cited by 60 publications

References 40 publications

Structure-property relationship for in vitro siRNA delivery performance of cationic 2-hydroxypropyl-β-cyclodextrin: PEG-PPG-PEG polyrotaxane vectors

Structure-property relationship for in vitro siRNA delivery performance of cationic 2-hydroxypropyl-β-cyclodextrin: PEG-PPG-PEG polyrotaxane vectors

Chain architecture and flexibility of α-cyclodextrin/PEG polyrotaxanes in dilute solutions

Recent advances in cyclodextrin delivery techniques

Contact Info

Product

Resources

About