Tailored Design of Au Nanoparticle-siRNA Carriers Utilizing Reversible Addition−Fragmentation Chain Transfer Polymers

Abstract

The facile synthesis of polymer-stabilized Au nanoparticles (AuNPs) capable of forming neutral, sterically stable complexes with small interfering RNA (siRNA) is reported. The amine-containing cationic block of poly(N-2-hydroxypropyl methacrylamide(70)-block-N-[3-(dimethylamino)propyl] methacrylamide(24)) [P(HPMA(70)-b-DMAPMA(24))] was utilized to promote the in situ reduction of Au(3+) to AuNPs and subsequently bind small interfering RNA, while the nonimmunogenic, hydrophilic block provided steric stabilization. The ratio of [DMAPMA](0)/[Au(3+)](0) utilized in the reduction reaction was found to be critical to the production of polymer-stabilized AuNPs capable of complexing siRNA. Significant protection ( approximately 100 times) against nucleases was demonstrated by enzymatic tests, while gene down-regulation experiments indicated successful delivery of siRNA to cancerous cells.

Salt-Responsive Polysulfabetaines from Acrylate and Acrylamide Precursors: Robust Stabilization of Metal Nanoparticles in Hyposalinity and Hypersalinity

“…This is likely due to the coordination of metal nanoparticles to the CO group. 59 Though theoretically one could expect the interaction of metal ions with other counterions present in the polymer, the aforementioned shift in the CO absorption frequency is an indication that the predominant mode of association between polymer and metal nanoparticles is 60,61 No change in absorption corresponding to the sulfate anion was noticed with the asymmetric stretching of SO appearing at 1028 cm −1 in both native and capped polysulfabetaines. This may be due to the fact that the interaction between the sulfate anion and quaternary ammonium species remained unperturbed.…”

Tuning PEGylation of mixed micelles to overcome intracellular and systemic siRNA delivery barriers

“…This phenomenon was used to measure the ability of the mixed micelles to protect siRNA against nuclease degradation as previously described [37,38]. Micelleplexes at a N+/P− ratio of 6 were diluted in 100 μL of dH 2 O to a final siRNA concentration of 500 nM and placed in a small volume quartz cuvette.…”

A new proton sponge polymer synthesized by RAFT polymerization for intracellular delivery of biotherapeutics

“…[20][21][22][23][24][25][26][27][28][29][30][31] Some of these polymers could be used efficiently to complex nucleic acid therapeutics and displayed to a certain degree endosome escaping ability possibly through the proton-sponge effect. 27,[29][30][31] A few polymers with proton-sponge capacity were also derived from functional polymer precursors such as oxazoline and pentauorophenyl ester polymers synthesized via RAFT polymerization. 22,32,33 In this study, we intended to synthesize a new, spermine/ spermidine-like polymer via RAFT polymerization as a potential endosomal escaping agent.…”