Nonionic Water-Soluble and Cytocompatible Poly(amide acrylate)s

Abstract

We report secondary amide side-chain-bearing polyacrylates with tunable aqueous solubility and cellular interaction. Redox-initiated reversible addition-fragmentation chain transfer polymerization of methylamide ethyl acrylate (MAmEA) and ethylamide ethyl acrylate (EAmEA) yielded well-defined homopolymers. P(MAmEA) and P(EAmEA) possess high glass-transition temperatures compared to the equivalent alkylated polyacrylates. P(EAmEA) showed a degree of polymerization and concentration-dependent lower critical solution temperature (LCST) behavior, which can be fine-tuned over a biologically relevant range through copolymerization of both monomers. No cytotoxicity against NIH 3T3 and RAW 264.7 cell lines was observed. Detailed cellular interaction studies revealed cell associations for P(MAmEA) similar to poly(N-acryloylmorpholine), a well-known nonionic water-soluble polymer and colocalization of both homopolymers with lysosomes. Due to the simple access of these monomers, the aqueous solubility, cytocompatibility, and cellular interaction of the homopolymers, and the possibility to combine them with a large number of acrylates, they hold great promise to become suitable building blocks for biomedical materials.

Tuning Cellular Interactions of Carboxylic Acid-Side-Chain-Containing Polyacrylates: The Role of Cyanine Dye Label and Side-Chain Type

“…P(E 1 ) is highly negatively charged due to the carboxylic acid groups (Table S3), while P(EAmEA), with its terminal ethyl amide side groups, is a nonionic polymer. 42 Moreover, when the experiment was performed at 4 °C, P(EAmEA) association with 3T3 cells was substantially inhibited in comparison to P(E 1 ). Thus, it can be concluded that the type of side chain significantly affects the cellular uptake mechanisms of the resulting polymers.…”

“…Subsequently, the ethyl (N-propionyl) side chain and acrylate functionality were introduced through amidation and esterification, respectively, as reported for their amide equivalents. 42 The same sequence of reactions was repeated using E 1t instead of tert-butyl acrylate to obtain E 2t . Noteworthy, the choice of solvent for the reaction of ethanolamine with E 1t was critical.…”

“…E 1t , the protected DP 1 monomer, was synthesized starting from tert -butyl acrylate, which was reacted with ethanolamine in a Michael addition reaction. Subsequently, the ethyl ( N -propionyl) side chain and acrylate functionality were introduced through amidation and esterification, respectively, as reported for their amide equivalents . The same sequence of reactions was repeated using E 1t instead of tert -butyl acrylate to obtain E 2t .…”

Poly(tertiary amide acrylate) Copolymers Inspired by Poly(2-oxazoline)s: Their Blood Compatibility and Hydration States

“…Tertiary amide alcohol was previously synthesized and then esterified by (meth)acryloyl chloride. The same strategy was employed to synthesize secondary amide acrylate in the recent work by Mahmud et al 27 Because the tertiary amide moiety is deemed the repeating unit of POXs, functionalization from 2-oxazolines seems feasible by combining the chemical properties of 2- oxazolines. Weber 28 reported three routes to functionalize (meth)acrylate with POX units with 2-oxazolines.…”

Adamantane Functionalized Poly(2-oxazoline)s with Broadly Tunable LCST-Behavior by Molecular Recognition

“…For LCST behavior in particular, the hydrophilic–hydrophobic balance in the polymer structure can be carefully optimized to tune the LCST behavior, or more specifically, the phase separation temperature or the cloud point temperature (T cp ) at a given polymer concentration. In this regard, numerous hydrophilic–hydrophobic monomer combinations have been explored for several biocompatible polymer classes, such as poly(acrylamides) [ 15 , 16 , 17 ], oligoethyleneglycol functional polymers [ 10 , 18 , 19 ], poly(amino acids), polypeptoids, and poly(2-alkyl-2-oxazoline)s (PAOx) [ 20 , 21 , 22 , 23 , 24 ], and they are subsequently exploited in tissue engineering or drug delivery contexts [ 25 , 26 , 27 , 28 , 29 , 30 ]. While tuning the LCST behavior by varying the relative ratio of hydrophilic to hydrophobic monomers might seem straightforward, several factors have to be taken into account, viz.…”