Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, People's Republic of China.
Nanotechnology. 2011 Dec 9;22(49):494012. doi: 10.1088/0957-4484/22/49/494012. Epub 2011 Nov 21.
A novel pH-responsive poly(amino acid) grafted with oligocation was prepared through the combination of ring-opening polymerization (ROP) and subsequent atom transfer radical polymerization (ATRP). Firstly, poly(γ-2-chloroethyl-L-glutamate) (PCELG) with a pendent 2-chloroethyl group was synthesized through ROP of γ-2-chloroethyl-L-glutamate N-carboxyanhydride (CELG NCA) using n-hexylamine as the initiator. Then, PCELG was used to initiate the ARTP of 2-aminoethyl methacrylate hydrochloride (AMA), yielding poly(L-glutamate)-graft-oligo(2-aminoethyl methacrylate hydrochloride) (PLG-g-OAMA). The pK(a) of PLG-g-OAMA was 7.3 established by the acid-base titration method. The amphiphilic poly(amino acid) could directly self-assemble into a vesicle in PBS. The vesicle was characterized by TEM and DLS. Hydrophilic DOX·HCl was loaded into the hollow core of the vesicle. The in vitro release behavior of DOX·HCl from the vesicle in PBS could be adjusted by the solution pH. In vitro cell experiments revealed that the vesicle could reduce the toxicity of the DOX·HCl. In addition, the preliminary gel retardation assay displayed that PLG-g-OAMA could efficiently bind DNA at a PLG-g-OAMA/DNA weight ratio of 0.3 or above, indicating its potential use as a gene carrier. More in-depth studies of the PLG-g-OAMA vesicle for drug and gene co-delivery in vitro and in vivo are in progress.
一种新型的 pH 响应性聚（氨基酸）接枝低聚物通过开环聚合（ROP）和随后的原子转移自由基聚合（ATRP）制备。首先，通过γ-2-氯代-L-谷氨酸 N-羧酸酐（CELG NCA）的 ROP，使用正己胺作为引发剂，合成了带有侧基 2-氯乙基的聚（γ-2-氯乙基-L-谷氨酸）（PCELG）。然后，PCELG 被用于引发 2-氨基乙基甲基丙烯酸盐酸盐（AMA）的 ATRP，得到聚（L-谷氨酸）-接枝-低聚（2-氨基乙基甲基丙烯酸盐酸盐）（PLG-g-OAMA）。通过酸碱滴定法确定 PLG-g-OAMA 的 pK（a）为 7.3。两亲性聚（氨基酸）可直接在 PBS 中自组装成囊泡。通过 TEM 和 DLS 对囊泡进行了表征。亲水性 DOX·HCl 被装载到囊泡的中空核中。DOX·HCl 从 PBS 中囊泡的体外释放行为可以通过溶液 pH 进行调节。体外细胞实验表明，囊泡可以降低 DOX·HCl 的毒性。此外，初步的凝胶阻滞实验表明，PLG-g-OAMA 在 PLG-g-OAMA/DNA 重量比为 0.3 或以上时可以有效地与 DNA 结合，表明其作为基因载体的潜在用途。正在深入研究 PLG-g-OAMA 囊泡在体外和体内用于药物和基因共递送的情况。
