Tianjin Key Laboratory of Biomedical Materials, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin300192, China.
Faculty of Material Science and Chemical Engineering, Ningbo University, Ningbo315211, China.
ACS Appl Mater Interfaces. 2023 Feb 15;15(6):7867-7877. doi: 10.1021/acsami.2c22267. Epub 2023 Feb 5.
Poly(-acryloyl glycinamide) (PNAGA) can form high-strength hydrogen bonds (H-bonds) through the dual amide motifs in the side chain, allowing the polymer to exhibit gelation behavior and an upper critical solution temperature (UCST) property. These features make PNAGA a candidate platform for biomedical devices. However, most applications focused on PNAGA hydrogels, while few focused on PNAGA nanoparticles. Improving the UCST tunability and bio-interfacial adhesion of the PNAGA nanoparticles may expand their applications in biomedical fields. To address the issues, we established a reactive H-bond-type P(NAGA--NAS) copolymer reversible addition-fragmentation chain transfer polymerization of NAGA and -acryloxysuccinimide (NAS) monomers. The UCST behaviors and the bio-interfacial adhesion toward the proteins and cells along with the potential application of the copolymer nanoparticles were investigated in detail. Taking advantage of the enhanced H-bonding and reactivity, the copolymer exhibited a tunable UCST in a broad temperature range, showing thermo-reversible transition between nanoparticles (PNPs) and soluble chains; the PNPs efficiently bonded proteins into nano-biohybrids while keeping the secondary structure of the protein, and more importantly, they also exhibited good adhesion ability to the cell membrane and significantly inhibited cell-specific propagation. These features suggest broad prospects for the P(NAGA--NAS) nanoparticles in the fields of biosensors, protein delivery, cell surface decoration, and cell-specific function regulation.
聚（丙烯酰基甘氨酰胺）（PNAGA）可以通过侧链中的双酰胺基序形成高强度氢键（H 键），使聚合物表现出凝胶行为和上临界溶解温度（UCST）特性。这些特性使 PNAGA 成为生物医学设备的候选平台。然而，大多数应用集中在 PNAGA 水凝胶上，而很少关注 PNAGA 纳米颗粒。提高 PNAGA 纳米颗粒的 UCST 可调性和生物界面附着力可能会扩大其在生物医学领域的应用。为了解决这些问题，我们建立了一种反应性氢键型 P（NAGA-NAS）共聚物，通过 NAGA 和 -丙烯酰氧基琥珀酰亚胺（NAS）单体的可逆加成-断裂链转移聚合。详细研究了共聚物纳米粒子的 UCST 行为和对蛋白质及细胞的生物界面附着力以及共聚物纳米粒子的潜在应用。利用增强的氢键和反应性，共聚物在较宽的温度范围内表现出可调的 UCST，显示出纳米颗粒（PNPs）和可溶性链之间的热可逆转变；PNPs 有效地将蛋白质键合到纳米生物杂种中，同时保持蛋白质的二级结构，更重要的是，它们对细胞膜也具有良好的附着力，并能显著抑制细胞特异性增殖。这些特性表明 P（NAGA-NAS）纳米粒子在生物传感器、蛋白质递送、细胞膜表面修饰和细胞特异性功能调节等领域具有广阔的前景。
