A direct comparison of linear and star-shaped poly(dimethylaminoethyl acrylate) polymers for polyplexation with DNA and cytotoxicity in cultured cell lines

Abstract

Poly[2-(Dimethylamino) ethyl acrylate] (PDMAEA) based polymers have been studied as potential gene delivery system. However, few reports emerging in literature suggesting that star-shaped PDMAEA based polymers are performing better in polyplexation with DNA, cytotoxicity and transfection, as compared to linear counterparts. Nonetheless, little evidences exist on direct comparison between the linear and star-shaped polymer structures. To address this, a series of new star-shaped PDMAEA polymers with linear counterparts were synthesised and directly compared their polyplexation with DNA and cytotoxicity in culture cell lines. The star-shaped PDMAEA polymers were synthesised using pentaerythritol tetrakis [2-(dodecylthiocarbonothioylthio)-2-methylpropionate] (4-arm DDMAT) RAFT agent in a “core-first” approach, whereas 2-(dodecylthiocarbonothioylthio)-2-methylpropionate was used to synthesise linear PDMAEA polymers. In order to investigate the effect of molar mass, both star-shaped and linear PDMAEA were synthesised in low (10kDa) and high (20kDa) molar mass. It must be noted here that the overall molar mass of the star-shaped polymer was equal to that of the linear counterparts. Interestingly, we found that the star-shaped polymer has slightly smaller hydrodynamic diameter (more compact) relative to linear counterparts, and importantly, star-shaped PDMAEA binds to DNA at much lower nitrogen to phosphate ratio (N/P ratio). However, the cytotoxicity studies in cultured 3T3 murine cell lines demonstrated that both star-shaped and linear counterparts have no toxicity at low 10kDa, but significantly toxic at higher 20kDa molar mass, this finding confirmed that the molar mass of PDMAEA play a key role in cytotoxicity effect, not variable polymer structures. Taken together, star-shaped PDMAEA binds more effectively to DNA than linear counterparts and showed no toxicity at 10kDa molar mass at variable polymer concentrations

Synthesis, characterization, and performance of a novel polycarboxylate superplasticizer with a crosslinked topological structure

“…As shown in Figure , TPC formed a crosslinked structure which had much stronger steric hindrance in contrast to CPC with linear comb‐like molecular chains. The steric hindrance effect provided by TPC's stereo structure could help to stabilize the dispersion, which is in accordance with the paste fluidity results . In addition, the crosslinked molecular structure could be broken in an alkali pore solution of cementitious system, the ester groups of crosslinker TMPTA were hydrolyzed into carboxyl groups .…”

Cationic dynamic covalent polymers for gene transfection

“…The results show that oligomers do indeed self-assemble when the polycondensation reaction is carried out at high concentration (typically > 50 mM), and that the resulting dynamers display multivalent binding to plasmid DNA in aqueous buffer as well as in biological serum. 160 Moreover, the acyl-hydrazone-based dynamers have been shown to be pH-sensitive and to undergo degradation at pH ≈ 5 corresponding to the pH of late endosomes, while remaining stable over much longer period of time at physiological pH. The second generation of linear dynamers includes modified amino acids and involve acyl-hydrazone and oxime condensation reactions for polymer formation (Fig.…”

Effects of Chemical Modifications on the Thermoresponsive Behavior of a PDMAEA-b-PNIPAM-b-POEGA Triblock Terpolymer

“…Among various thermoresponsive polymers, PNIPAM (poly(N-isopropylacrylamide))-based polymers have received great interest due to its phase transition temperature being very close to human body temperature (LCST of 32 • C) and thus render it a prominent candidate for biomedical applications [46][47][48][49][50][51][52][53]. Moreover, pH-responsive polymers are of outstanding significance owing to their cationic nature and their pH swelling/deswelling properties in aqueous media, which are properties that make them valuable candidates in the field of gene therapy [54][55][56][57][58][59]. The poly(2-(dimethylamino)ethyl acrylate-based (PDMAEA) polymers, the acrylate version of poly(2-(dimethylamino)ethyl methacrylate (PDMAEMA), respond to pH variations since PDMAEA presents a pKa = 8.41) [60], and they are gaining extensive scientific attention because of their potential utilization as non-viral synthetic carriers for gene delivery.…”