Nonviral Plasmid DNA Carriers Based on N,N′-Dimethylaminoethyl Methacrylate and Di(ethylene glycol) Methyl Ether Methacrylate Star Copolymers

Abstract

Star polymers with random and block copolymer arms made of cationic N,N'-dimethylaminoethyl methacrylate (DMAEMA) and nonionic di(ethylene glycol) methyl ether methacrylate (DEGMA) were synthesized via atom transfer radical polymerization (ATRP) and used for the delivery of plasmid DNA in gene therapy. All stars were able to form polyplexes with plasmid DNA. The structure and size of the polyplexes were precisely determined using light scattering and cryo-TEM microscopy. The hydrodynamic radius of a complex of DNA with star was dependent on the architecture of the star arms, the DEGMA content and the number of amino groups in the star compared to the number of phosphate groups of the nucleic acid (N/P ratio). The smallest polyplexes (Rh90°∼50 nm) with positive zeta potentials (∼15 mV) were formed of stars with N/P=6. The introduction of DEGMA into the star structure caused a decrease of polyplex cytotoxicity in comparison to DMAEMA homopolymer stars. The overall transfection efficiency using HT-1080 cells showed that the studied systems are prospective gene delivery agents. The most promising results were obtained for stars with random copolymer arms of high DEGMA content.

Synthesis, Characterization and Cytotoxicity of Novel Thermoresponsive Star Copolymers of N,N′-Dimethylaminoethyl Methacrylate and Hydroxyl-Bearing Oligo(Ethylene Glycol) Methacrylate

“…Star polymers with arms consisting of N , N -dimethylaminoethyl methacrylate and oligo(ethylene glycol) methacrylate (OEGMA) with different numbers of ethylene glycol units could be synthesized using different polymerization techniques, e.g., ATRP [9,10,11,12], reversible addition-fragmentation chain transfer (RAFT) [13,14] or group transfer polymerization (GTP) [15]. Both the “core first” and “arm first” approaches have been used to synthesize these structures by the aforementioned polymerizations.…”

“…Both the “core first” and “arm first” approaches have been used to synthesize these structures by the aforementioned polymerizations. In the “core first” method, the multifunctional compound initiates the polymerization of the monomers [9,11,12]. This strategy facilitates the formation of well-defined polymers with precisely controlled numbers of arms and chain lengths.…”

“…Of the synthesized DMAEMA- co -OEGMA star polymers, mainly OEGMA derivatives with methyl or ethyl end groups have been prepared [10,11,12,14,15]. Such stars have been used as nucleic acid carriers in gene therapy, and the cationic amino groups of these polymers condense DNA or RNA into so-called polyplexes, while poly[oligo(ethylene glycol) methacrylate] (POEGMA) segments are responsible for the increase in the biocompatibility [10,12,15].…”

Polymers in medicine direction of development

“…Polymeric structures resembling micelle, which are often used as drug carriers, are polymeric stars, or molecules with macromolecular arms covalently linked with a central unit -the core. Their carrier functions were widely described [10][11][12][13].…”

Nanolayers of Poly(N,N′-Dimethylaminoethyl Methacrylate) with a Star Topology and Their Antibacterial Activity

“…Various cationic polymers show high levels of sustained antibacterial activity, as described in several reviews [24][25][26][27][28][29][30]. Examples of such polymers include poly (4-vinylpyridine) [4,31], polyethylenimine [32,33], and poly(N,N -dimethylaminoethyl methacrylate) [3,34,35]. Functional amino groups of these polymers are often quaternized to enhance their bactericidal activity [31,34,36,37], as they are capable of interacting with the negatively charged cell walls of bacteria.…”