Preparation of Cationic Nanogels for Nucleic Acid Delivery

Abstract

Cationic nanogels with site-selected functionality were designed for the delivery of nucleic acid payloads targeting numerous therapeutic applications. Functional cationic nanogels containing quaternized 2-(dimethylamino)ethyl methacrylate and a cross-linker with reducible disulfide moieties (qNG) were prepared by activators generated by electron transfer (AGET) atom transfer radical polymerization (ATRP) in an inverse miniemulsion. Polyplex formation between the qNG and nucleic acid exemplified by plasmid DNA (pDNA) and short interfering RNA (siRNA duplexes) were evaluated. The delivery of polyplexes was optimized for the delivery of pDNA and siRNA to the Drosophila Schneider 2 (S2) cell-line. The qNG/nucleic acid (i.e., siRNA and pDNA) polyplexes were found to be highly effective in their capabilities to deliver their respective payloads.

Cationic Nanogel-mediated Runx2 and Osterix siRNA Delivery Decreases Mineralization in MC3T3 Cells

“…The nanogels were purified using dialysis and characterized using dynamic light scattering and zeta potential analysis. Further details on nanogel synthesis and characterization can be found in Averick et al [6].…”

Controlled Radical Polymerization: State-of-the-Art in 2014

“…In the former case, polymers grown from nanoparticles or flat surfaces, dramatically change particles stability, dispersibility and thermomechanical properties, in addition to tremendously enhancing lubricity, antifouling or antibacterial properties (53)(54)(55)(56)(57)(58)(59)(60)(61). Hybrids with proteins or nucleic acids increase stability of proteins in harsh environments, (including temperature, pH, and salts) assist in delivery of genes, and can be used in advanced drug delivery (45,(62)(63)(64)(65)(66)(67)(68)(69)(70)(71).…”

Nanogel-Mediated RNAi Against Runx2 and Osx Inhibits Osteogenic Differentiation in Constitutively Active BMPR1A Osteoblasts

“…Further details on nanogel NSP synthesis and characterization can be found in the following reference. 19 …”

“…16–18 We have produced cationic nanogel nanostructured polymers (nanogel NSPs) by atom transfer radical polymerization (ATRP) to produce a bioresponsive, interconnected polymeric network for siRNA delivery. 19 This effort integrates several strategies for efficient siRNA delivery, including PEGylation, steric shielding of siRNAs, built-in features for endosomal escape, and stimuli-specific degradation mechanisms. We previously reported that nanogel NSPs demonstrate minimal dose-dependent cytotoxicity, efficient siRNA binding and release, and internalization into mammalian cells.…”