This article describes a novel reduction degradable supramolecular nanoparticle gene delivery system via host–guest interaction based on cyclodextrin-conjugated polyaspartamide with disulfide linkage (Pasp-SS-CD) and adamantyl-terminated polyethylenimine (Ad₄-PEI). The reduction responsiveness of Pasp-SS-CD and the Pasp-SS-CD/Ad₄-PEI/pDNA supramolecular nanoparticles (SNPs) in the presence of DL-dithiothreitol (DTT) was confirmed by SEC-MALLS and DLS analysis, respectively. Compared with the Ad₄-PEI/pDNA polyplexes, the bioreducible supramolecular polycation/pDNA polyplexes exhibited smaller particle size, slightly higher zeta potential, lower cytotoxicity and hemolysis ratio, improved cellular internalization and higher gene transfection efficiency. It was found that introducing Pasp-SS-CD to assemble Ad₄-PEI could substantially enhance the tolerance of protein adsorption and maintain the gene transfer capacity of polycationic carriers, which might be beneficial for in vivo use. In addition, the cellular uptake pathway of the supramolecular polycation/pDNA polyplexes was investigated using different uptake inhibitors. The present study demonstrates that the proper assembly of cyclodextrin-conjugated polyaspartamide and adamantyl-terminated polyethylenimine is an effective strategy for the production of a new gene delivery system.

中文翻译：

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基于环糊精偶联的聚天冬酰胺和金刚烷基封端的聚乙烯亚胺的生物可还原的超分子纳米基因传递系统†

本文介绍了一种新型的可降解降解的超分子纳米颗粒基因递送系统，该系统基于具有二硫键的环糊精偶联的聚天冬酰胺（Pasp-SS-CD）和金刚烷基封端的聚乙烯亚胺（Ad ₄ -PEI），通过宿主-客体相互作用。分别通过SEC-MALLS和DLS分析证实了在DL-二硫苏糖醇（DTT）存在下Pasp-SS-CD和Pasp-SS-CD / Ad ₄ -PEI / pDNA超分子纳米颗粒（SNP）的还原响应性。与广告₄相比-可生物还原的超分子聚阳离子/ pDNA复合物-PEI / pDNA复合物显示出较小的粒径，稍高的zeta电位，较低的细胞毒性和溶血比，改善的细胞内在化和较高的基因转染效率。发现引入Pasp-SS-CD组装Ad ₄ -PEI可以大大提高蛋白质吸附的耐受性并保持聚阳离子载体的基因转移能力，这可能对体内有益采用。另外，使用不同的摄取抑制剂研究了超分子聚阳离子/ pDNA多聚体的细胞摄取途径。本研究表明，环糊精偶联的聚天冬酰胺和金刚烷基封端的聚乙烯亚胺的正确组装是生产新基因递送系统的有效策略。