Decationized crosslinked polyplexes for redox-triggered gene delivery

Novo, Luís; Gaal, Ethlinn V.B. van; Mastrobattista, Enrico; Nostrum, Cornelus F. van; Hennink, Wim E.

doi:10.1016/j.jconrel.2013.03.035

Cited by 40 publications

(85 citation statements)

References 63 publications

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“…Additionally, as anticipated, decationized polyplexes have shown an excellent safety profile and extensive in vitro tests have shown that decationized polyplexes do not interfere with cell viability nor induce membrane destabilization at any of the doses tested [19,20]. Furthermore, the neutral block copolymer pHP--PEG that forms decationized polyplexes showed excellent cytocompatibility upon incubation with HUVEC cells.…”

Section: Decationized Polyplexes Propertiesmentioning

confidence: 56%

“…Decationized polyplexes generally have a size of~120 nm and a slightly negative zeta-potential (-5mV) (vs~120 nm and +10 mV for the pHDP--PEG cationic polyplexes), excellent colloidal stability and triggered pDNA release in a reductive environment [19]. Another important characteristic of decationized polyplexes is their low degree of nonspecific cell uptake, which is a requirement for targeted therapies by using cell-specific ligands that are coupled on the surface of the polyplexes.…”

Section: Decationized Polyplexes Propertiesmentioning

confidence: 99%

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Decationized polyplexes for gene delivery

Novo¹,

Mastrobattista²,

Nostrum³

et al. 2014

Expert Opinion on Drug Delivery

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Section: Decationized Polyplexes Propertiesmentioning

confidence: 56%

Section: Decationized Polyplexes Propertiesmentioning

confidence: 99%

Decationized polyplexes for gene delivery

Novo¹,

Mastrobattista²,

Nostrum³

et al. 2014

Expert Opinion on Drug Delivery

Self Cite

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“…Alternatively, disulfi de cross-linking could be utilized by them for redox-triggered degradation and pDNA release under reductive-responsive conditions of the cytoplasm. [ 14 ] This approach was also utilized by Matyjaszewski and co-workers [ 15,16 ] to synthesize PEG-based nanogels for siRNA delivery, where the cationic cores were stabilized by disulfi de moieties.…”

Section: Introductionmentioning

confidence: 99%

Degradable Cationic Nanohydrogel Particles for Stimuli‐Responsive Release of siRNA

Nuhn

Braun

Overhoff

et al. 2014

Macromol. Rapid Commun.

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Well-defined nanogels have become quite attractive as safe and stable carriers for siRNA delivery. However, to avoid nanoparticle accumulation, they need to provide a stimuli-responsive degradation mechanism that can be activated at the payload's site of action. In this work, the synthetic concept for generating well-defined nanohydrogel particles is extended to incorporate disulfide cross-linkers into a cationic nanonetwork for redox-triggered release of oligonucleotide payload as well as nanoparticle degradation under reductive conditions of the cytoplasm. Therefore, a novel disulfide-modified spermine cross-linker is designed that both allows disassembly of the nanogel as well as removal of cationic charge from residual polymer fragments. The degradation process is monitored by scanning electron microscopy (SEM) and fluorescence correlation spectroscopy (FCS). Moreover, siRNA release is analyzed by agarose gel electrophoresis and a fluorescent RNA detection assay. The results exemplify the versatility of the applied nanogel manufacturing process, which allows alternative stimuli-responsive core cross-linkers to be integrated for triggered oligonucleotide release as well as effective biodegradation for reduced nanotoxicity.

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“…cleavage of single-strand crgD-sirNa conjugates in a reductive environment According to the reported concentrations of DTT (10-300 mM); [35][36][37][38][39][40] we used 100 mM of DTT to detect the cleavage of disulfide bond. The reaction was allowed to proceed at 37°C for 2 h, which was stopped by immediately storing the conjugates at -80°C until analysis.…”

Section: Western Blot Analysismentioning

confidence: 99%

Reductive nanocomplex encapsulation of cRGD-siRNA conjugates for enhanced targeting to cancer cells

Zhou¹,

Liu²,

Zhang³

et al. 2017

IJN

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In this study, through covalent conjugation and lipid material entrapment, a combined modification strategy was established for effective delivery of small interfering RNA (siRNA). Single strands of siRNA targeting to BRAF V600E gene (siMB3) conjugated with cRGD peptide at 3′-terminus or 5′-terminus via cleavable disulfide bond was synthesized and then annealed with corresponding strands to obtain single and bis-cRGD-siRNA conjugates. A cationic lipid material (CLD) developed by our laboratory was mixed with the conjugates to generate nanocomplexes; their uniformity and electrical property were revealed by particle size and zeta potential measurement. Compared with CLD/siBraf, CLD/cRGD-siBraf achieved higher cell uptake and more excellent tumor-targeting ability, especially 21 (sense-5′/antisense-3″-cRGD-congjugate) nanocomplex. Moreover, they can regulate multiple pathways to varying degree and reduce acidification of endosome. Compared with the gene silencing of different conjugates, single or bis-cRGD-conjugated siRNA showed little differences except 22 (5/5) which cRGD was conjugated at 5′-terminus of antisense strand and sense strand. However bis-cRGD conjugate 21 nanocomplex exhibited better specific target gene silencing at multiple time points. Furthermore, the serum stabilities of the bis-cRGD conjugates were higher than those of the single-cRGD conjugates. In conclusion, all these data suggested that CLD/bis-conjugates, especially CLD/ 21 , can be an effective system for delivery of siRNA to target BRAF V600E gene for therapy of melanoma.

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Decationized crosslinked polyplexes for redox-triggered gene delivery

Cited by 40 publications

References 63 publications

Decationized polyplexes for gene delivery

Decationized polyplexes for gene delivery

Degradable Cationic Nanohydrogel Particles for Stimuli‐Responsive Release of siRNA

Reductive nanocomplex encapsulation of cRGD-siRNA conjugates for enhanced targeting to cancer cells

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