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A biodegradable poly(amido amine) based on the antimicrobial polymer polyhexamethylene biguanide for efficient and safe gene delivery.
Colloids and Surfaces B: Biointerfaces ( IF 5.4 ) Pub Date : 2019-07-09 , DOI: 10.1016/j.colsurfb.2019.110355 Haonan Xing 1 , Lin Cheng 1 , Mei Lu 1 , Hui Liu 1 , Lang Lang 1 , Tianzhi Yang 2 , Xiaoyun Zhao 3 , Hui Xu 1 , Li Yang 1 , Pingtian Ding 1
Colloids and Surfaces B: Biointerfaces ( IF 5.4 ) Pub Date : 2019-07-09 , DOI: 10.1016/j.colsurfb.2019.110355 Haonan Xing 1 , Lin Cheng 1 , Mei Lu 1 , Hui Liu 1 , Lang Lang 1 , Tianzhi Yang 2 , Xiaoyun Zhao 3 , Hui Xu 1 , Li Yang 1 , Pingtian Ding 1
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Inspired by the excellent membrane affinity of antimicrobial polymers, we synthesized a novel biodegradable poly(amino amine) polymer with pendent side chains that mimic the widely used biocide polyhexamethylene biguanide (PHMB) for gene delivery. Michael addition polymerization was utilized to form the polymer scaffold between N,N'-cystaminebisacrylamide (CBA) and N-Boc-1,6-diaminohexane (Boc-DAH) followed by N-Boc deprotection. Then the exposed primary amino groups were partly (about 75%) transformed into biguanide by an addition reaction with dicyandiamide to obtain the final product CBA-DAH-biguanide (CBA-DAH-BG). The polymer CBA-DAH-BG was able to condense plasmid DNA (pDNA) into nano-sized (<200 nm), positively-charged (>35 mV) polyplexes that were well resistant to heparin and DNase I. Rapid DNA release was observed in the presence of dithiothreitol (DTT), indicating that CBA-DAH-BG was equipped with biodegradability by the cleavage of disulfide bonds, which was helpful for unpacking DNA and decreasing cytotoxicity. CBA-DAH-BG/pDNA polyplexes were characterized by efficient cellular uptake efficacy, extremely low cytotoxicity, and high transfection efficiency in two cell lines (i.e., NIH/3T3 and U87 MG), compared to 25 kDa polyethyleneimine (PEI) and the intermediate product CBA-DAH that were both devoid of biguanide groups. Of note, clathrin-mediated endocytosis and lipid rafts played an important role in the internalization of the polyplexes. Taken together, this strategy described herein may represent an innovative avenue for the design of more advanced nonviral gene vectors with high transfection efficiency and biocompatibility.
中文翻译：
基于抗菌聚合物聚六亚甲基双胍的可生物降解的聚（酰胺胺），可高效安全地传递基因。
受抗菌聚合物优异的膜亲和力的启发，我们合成了一种新型的可生物降解的聚（氨基胺）聚合物，该聚合物具有侧链，可模仿广泛使用的杀生物剂聚六亚甲基双胍（PHMB）进行基因传递。利用迈克尔加成聚合反应在N，N'-胱胺双丙烯酰胺（CBA）和N-Boc-1,6-二氨基己烷（Boc-DAH）之间形成聚合物支架，然后进行N-Boc脱保护。然后通过与双氰胺的加成反应将暴露的伯氨基部分地（约75％）转化成双胍，以获得最终产物CBA-DAH-双胍（CBA-DAH-BG）。聚合物CBA-DAH-BG能够将质粒DNA（pDNA）浓缩成对肝素和DNase I具有良好抗性的纳米级（<200 nm）带正电（> 35 mV）的复合体。在二硫苏糖醇（DTT）的存在下观察到DNA的快速释放，表明CBA-DAH-BG通过二硫键的裂解具有生物可降解性，这有助于解开DNA并降低细胞毒性。与25 kDa聚乙烯亚胺（PEI）和中间体相比，CBA-DAH-BG / pDNA多聚体的特征是在两种细胞系（即NIH / 3T3和U87 MG）中具有有效的细胞吸收功效，极低的细胞毒性和高转染效率。均不含双胍类的产物CBA-DAH。值得注意的是，网格蛋白介导的内吞作用和脂质筏在多聚体的内在化中起重要作用。在一起
更新日期：2019-07-09
中文翻译：
基于抗菌聚合物聚六亚甲基双胍的可生物降解的聚（酰胺胺），可高效安全地传递基因。
受抗菌聚合物优异的膜亲和力的启发，我们合成了一种新型的可生物降解的聚（氨基胺）聚合物，该聚合物具有侧链，可模仿广泛使用的杀生物剂聚六亚甲基双胍（PHMB）进行基因传递。利用迈克尔加成聚合反应在N，N'-胱胺双丙烯酰胺（CBA）和N-Boc-1,6-二氨基己烷（Boc-DAH）之间形成聚合物支架，然后进行N-Boc脱保护。然后通过与双氰胺的加成反应将暴露的伯氨基部分地（约75％）转化成双胍，以获得最终产物CBA-DAH-双胍（CBA-DAH-BG）。聚合物CBA-DAH-BG能够将质粒DNA（pDNA）浓缩成对肝素和DNase I具有良好抗性的纳米级（<200 nm）带正电（> 35 mV）的复合体。在二硫苏糖醇（DTT）的存在下观察到DNA的快速释放，表明CBA-DAH-BG通过二硫键的裂解具有生物可降解性，这有助于解开DNA并降低细胞毒性。与25 kDa聚乙烯亚胺（PEI）和中间体相比，CBA-DAH-BG / pDNA多聚体的特征是在两种细胞系（即NIH / 3T3和U87 MG）中具有有效的细胞吸收功效，极低的细胞毒性和高转染效率。均不含双胍类的产物CBA-DAH。值得注意的是，网格蛋白介导的内吞作用和脂质筏在多聚体的内在化中起重要作用。在一起
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