Hong Y. Cho

Preparation of cationic nanogels for nucleic acid delivery.

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.

Star polymers with a cationic core prepared by ATRP for cellular nucleic acids delivery.

Poly(ethylene glycol) (PEG)-based star polymers with a cationic core were prepared by atom transfer radical polymerization (ATRP) for in vitro nucleic acid (NA) delivery. The star polymers were synthesized by ATRP of 2-(dimethylamino)ethyl methacrylate (DMAEMA) and ethylene glycol dimethacrylate (EGDMA). Star polymers were characterized by gel permeation chromatography, zeta potential, and dynamic light scattering. These star polymers were combined with either plasmid DNA (pDNA) or short interfering RNA (siRNA) duplexes to form polyplexes for intracellular delivery. These polyplexes with either siRNA or pDNA were highly effective in NA delivery, particularly at relatively low star polymer weight or molar ratios, highlighting the importance of NA release in efficient delivery systems.

Photo-Cross-Linkable Thermoresponsive Star Polymers Designed for Control of Cell-Surface Interactions

Star polymers with thermoresponsive arms, consisting of 2-(2-methoxyethoxy)ethyl methacrylate (MEO₂MA) and oligo(ethylene glycol) methacrylate with ~4 ethylene oxide units (OEOMA₃₀₀, M(n) = 300), were synthesized via atom transfer radical polymerization (ATRP). 25% of the arms contained benzophenone chain-end functionality at the star periphery. A mixture of linear poly(MEO₂MA-co-OEOMA₃₀₀)-Br macroinitiators without and with benzophenone end-group macroinitiators were (MI and Bzp-MI, respectively) cross-linked with ethylene glycol dimethacrylate to form star polymers. Formation of star polymers was monitored by GPC, and the presence of benzophenone functionality in the stars was confirmed by ¹H NMR. The UV-vis spectroscopy revealed that the star polymers exhibit the low critical solution temperature (LCST) at 27 °C, slightly lower than LCST of either MI or Bzp-MI. Commercially available tissue culture grade polystyrene surface was modified by depositing a thin film of functionalized stars and UV cross-linking (λ = 365 nm). The star polymers covalently attached onto surfaces allowed a control of cell shrinkage and attachment in response to temperature changes.