Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University (TWIns), Shinjuku, Tokyo 162-8666, Japan.
Colloids Surf B Biointerfaces. 2012 Nov 1;99:12-9. doi: 10.1016/j.colsurfb.2011.09.028. Epub 2011 Sep 19.
Diblock copolymer comprising thermoresponsive poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide) (PIPAAm-co-DMAAm) and hydrophobic poly(benzyl methacrylate) blocks was prepared by reversible addition-fragmentation chain transfer radical polymerization. Terminal functionalization of thermoresponsive blocks with either pH-responsive sulfadimethoxine (SD) or hydroxyl groups was performed through coupling reactions with thiol groups exposed by the aminolysis of dithiobenzoate groups located at P(IPAAm-co-DMAAm) termini. Outermost surface functionalized polymeric micelles were formed through the multi-assemblies of end-functional diblock copolymers with low critical micelle concentration (3.1-3.3 mg/L) regardless of their terminal groups. Variety of outermost surface functional groups had little influence on nano-scale diameters of approximately 19 nm at various pH values. Although the zeta-potentials of nonionic (phenyl and hydroxyl) surface micelles were independent of pH values ranged 8.1-5.4, those of SD-surface polymeric micelles changed from -12 to -4 mV with reducing pH value, which caused by the protonation of surface SD units (pK(a)=6.2). In addition, lower critical solution temperature (LCST) of SD-surface micelles significantly shifted from 38.6 to 22.6 °C with lowering pH from 5.4 to 8.1. These pH-induced lower LCST shifts were caused by extremely increasing surface hydrophobicity through the charge neutralization of SD moieties and the subsequent promoted dehydration of corona-forming polymer chains. These results indicated that the phase transition behavior of thermoresponsive nano-micelles was particularly controlled by modulating the properties of outermost surface chemistry via specific signals (e.g., pH, light, and biomolecular interaction).
由温敏性聚（N-异丙基丙烯酰胺-co-N,N-二甲基丙烯酰胺）（PIPAAm-co-DMAAm）和疏水性聚（苄基甲基丙烯酸酯）嵌段组成的两亲嵌段共聚物通过可逆加成-断裂链转移自由基聚合制备。通过与巯基暴露的酰胺化反应，将温敏嵌段的端基功能化为 pH 响应磺胺二甲氧嘧啶（SD）或羟基。由二硫代苯甲酸酯基在 P(IPAAm-co-DMAAm)末端的氨解产生的巯基。具有低临界胶束浓度（3.1-3.3 mg/L）的端基功能化两亲嵌段共聚物的多组装形成了最外层表面功能化的聚合物胶束，而与它们的端基无关。各种最外层表面官能团在各种 pH 值下对大约 19nm 的纳米级直径几乎没有影响。尽管非离子（苯基和羟基）表面胶束的 ζ-电位与 pH 值 8.1-5.4 无关，但 SD-表面聚合物胶束的 ζ-电位随 pH 值的降低从-12 变为-4mV，这是由于表面 SD 单元的质子化（pK(a)=6.2）。此外，SD-表面胶束的较低临界溶液温度（LCST）从 38.6 显著降低至 22.6°C，pH 值从 5.4 降低至 8.1。这些 pH 诱导的较低 LCST 位移是由于 SD 部分的电荷中和以及随后促进冠形成聚合物链的脱水，从而极大地增加了表面疏水性。这些结果表明，通过通过特定信号（例如 pH、光和生物分子相互作用）调节最外层表面化学性质，可以特别控制温敏纳米胶束的相转变行为。
