We have developed a strategy for the preparation of redox-responsive PEG–PLA-based nanoparticles containing disulfide bonds that can be disassembled in the presence of cellular concentrations of glutathione. Functionalized poly(lactide)s were prepared by ring-opening copolymerization of l-lactide and 3-methyl-6-(tritylthiomethyl)-1,4-dioxane-2,5-dione, a monomer bearing a pendant trityl-thiol group, followed by the postpolymerization modification of trityl-thiol into pyridyl disulfide groups. Polymeric networks composed of PLA and PEG blocks linked by disulfide bonds were prepared by a disulfide exchange reaction between the functionalized PLAs and telechelic PEG having thiol groups at both ends, HS-PEG-SH, in DMF. When dialyzed against water, they assembled into dispersible nanoparticles, with a flowerlike structure having a hydrophobic core and a hydrophilic shell, with sizes in the range 167–300 nm that are suitable for drug delivery. The effects of the number of functional groups, molecular weight, and concentration on the nanoparticle size were evaluated. The stability of the nanoparticles after dilution and the redox-responsive behavior in the presence of different concentrations of glutathione were assessed. The hydrophobic molecule Nile red could be encapsulated in the nanoparticles and then released in the presence of glutathione at cellular concentration.

中文翻译：

---

氧化还原反应性二硫键交联的PLA–PEG纳米粒子

我们已经开发出了一种策略，用于制备基于氧化还原反应的基于PEG-PLA的纳米颗粒，该纳米颗粒含有二硫键，可以在细胞浓度的谷胱甘肽存在的情况下将其分解。通过将l的开环共聚反应制备官能化的聚丙交酯。-丙交酯和3-甲基-6-（三苯甲基硫甲基）-1,4-二恶烷-2,5-二酮（带有三苯甲基硫醇侧基的单体），然后将三苯甲基硫醇后聚合改性为吡啶基二硫基。通过功能化的PLA和两端都有硫醇基的远螯PEG（HS-PEG-SH）在DMF中进行二硫键交换反应，可以制备由通过二硫键连接的PLA和PEG嵌段组成的聚合物网络。当用水透析时，它们组装成可分散的纳米颗粒，其花状结构具有疏水核和亲水壳，尺寸在167-300 nm之间，适合于药物输送。评估了官能团数，分子量和浓度对纳米颗粒尺寸的影响。评估了稀释后纳米颗粒的稳定性以及在不同浓度的谷胱甘肽存在下的氧化还原响应行为。疏水分子尼罗红可以被包封在纳米颗粒中，然后在谷胱甘肽存在下以细胞浓度释放。