Dual-Temperature-Responsive Microgels from a Zwitterionic Functional Graft Copolymer with Superior Protein Repelling Property

Abstract

In this work, we developed a synthetic strategy to synthesize dual-temperature-responsive low surface fouling zwitterionic microgels. Statistical poly­(N-vinylcaprolactam-co-glycidyl methacrylate) copolymers were synthesized by RAFT polymerization and post-modified by thiol-epoxy click reaction with thiol end-group-modified poly­(sulfobetaine) macro-RAFT (PSB-SH) to obtain poly­(N-vinylcaprolactam-co-glycidyl methacrylate)-graft-poly­(sulfobetaine) (PVCL-co-PGMA-g-PSB) graft copolymers. Synthesized graft copolymers were cross-linked by diamine cross-linker in water-in-oil (w/o) inverse mini-emulsion to obtain zwitterionic microgels. Using this approach, we synthesized microgels with unique microstructure, high loading and uniform distribution of poly­(sulfobetaine) chains, which exhibits tunable dual-volume phase transition temperatures. The microgels also showed excellent antifouling property reflected in strongly reduced protein absorption on a microgel-coated surface observed in real time by a Quartz Crystal Microbalance with Dissipation (QCM-D) monitoring experiment with continuous flow of protein solution. Therefore, this kind of zwitterionic microgel can be potentially used for temperature-triggered drug delivery and anti-bioadhesion coating material as well.

Thermoresponsive zwitterionic poly(phosphobetaine) microgels: Effect of macro‐RAFT chain length and cross‐linker molecular weight on their antifouling properties

“…Similarly, the LCST transition was also increased because swollen PMPC chains formed a strong hydration layer to resist the collapse of the crosslinked PVCL network easily (see Figure 5E). 35 The effect of the variation of the cross‐linker molecular weight on thermoresponsive behavior was also noticed. Using higher molecular weight PEG‐NH 2 cross‐linker (10,000 g/mol), the synthesized microgels (MG‐10K10X) showed a shifting of both UCST and LCST towards relatively lower temperatures as PMPC chains could only stretch out to a lower extent, because the PVG copolymer chains are held together in a more compact manner compared to the cross‐linkers with lower molecular weight (3000 g/mol).…”

“…The RAFT end‐group removal was further confirmed from UV–vis studies. The presence of phenyl group at the tail‐end of PMPC macro‐RAFT was shown by a strong absorption peak at 305 nm (π‐π* transition), 35 which disappeared upon cleavage of the RAFT end‐group by NaBH 4 reduction (see Figure 3C). In some cases, unfavorable reaction conditions may lead to the oxidative dimerization of thiol to disulfide (‐S‐S‐) linkage 38 and might require extra steps to recover the thiol‐ended polymer product, that is, using dithiothreitol (DTT) as a reducing agent.…”

“…Previously, Schröder et al synthesized microgels based on sulfobetaine with differently sized vinyllactam rings in w/o inverse mini‐emulsion polymerization 33 . Recently, we have reported PVCL‐based zwitterionic sulfobetaine microgels via macro‐RAFT approach in both precipitation polymerization and inverse mini‐emulsion technique 34,35 . Recently, Tian et al have reported the synthesis of redox‐responsive bio‐degradable zwitterionic PMPC nanogels with a diselenide type cross‐linker via reflux precipitation polymerization and studied the drug release in the presence of different oxidant and reductants, which led to the degradation of the cross‐linked network in the nanogels 29 …”

Nanogels: A novel approach in antimicrobial delivery systems and antimicrobial coatings

“…Addressing the temperature-responsive characteristics of nanogels, Saha and co-workers investigated a synthetic strategy to obtain zwitterionic nanogels that exhibit tunable dual-VPTT [ 283 ]. These nanogels were covalently bound on activated SiO 2 quartz sensors, and the anti-fouling activity was tested by quartz crystal microbalance-dissipation (QCM-D) experiments under a flow of protein solution.…”

“… Coating Applications Nanogels Ref. Reduced protein adhesion p (NIPAM) nanogels cross-linked with PEG diacrylate [ 27 ] Prevented bacteria attachment on the surface for biomaterials p (NIPMAM) nanogel coatings [ 29 ] Allowed cell adhesion and spreading p (NIPAM) nanogels [ 268 ] Antifouling surface towards bacteria on the surface p (NIPAM -co- VFc) nanogels [ 281 ] Decreased bacterial attachment and biofilm thickness for biomaterials PSBMA/PES nanogels [ 282 ] Reduced protein adsorption SiO 2 quartz sensors (PVCL-co-PGMA-g-PSB) zwitterionic nanogels [ 283 ] Antifouling properties for biosensors p (NIPMAM) nanogels [ 284 ] Antifouling properties and self-cleaning performance for the membrane (P4VP) nanogels [ 285 ] Inhibited the bacterial adhesion and the protein adsorption on the membrane P (AA-VP) and (P (AMPS-AM)) nanogels [ 286 , 287 ] Antifouling and antibacterial membrane surface poly (sulfobetaine methacrylate -co- 2-aminoethyl methacrylate) nanogels by cross-linking of eugenol-modified chitosan [ 288 ] Antifouling and antimicrobial surface coatings Peptide-loaded poly (ethyl acrylate -co- methacrylic acid) nanogels [ 290 ] ...…”