Exploring the outer limits of polyplexes.
Exploring the outer limits of polyplexes.
复制标题
探索复合物的外部极限。
DOI：
10.1016/j.bbrc.2023.08.023
复制
发表时间：
2023
影响因子：
3.1
通讯作者：
Mixson,AJames
中科院分区：
文献类型：
--
作者：
Agrawal,A;Leng,Q;Imtiyaz,Z;Mixson,AJames
含组氨酸的聚合物在体外和体内核酸运输方面显示出前景。除了 pH 缓冲组氨酸成分外，聚合物通常还含有生理 pH 下的质子化成分，例如赖氨酸。这些复合物通常通过增强的渗透性和保留而在肿瘤中积累，这在临床试验中被证明是令人失望的。我们目前比较了两种组氨酸-赖氨酸 (HK) 肽复合物的神经毡蛋白-1 介导的体内质粒转运。虽然聚合的 HK (H2KC-48) 聚合复合物在体外明显优于单体 HK (H2K) 聚合复合物，但这两种 HK 聚合复合物在各种肽和质粒比例下都能有效转染肿瘤异种移植物。然而，低肽/DNA比率的多聚体比高比率的多聚体具有更高的肿瘤转染和特异性。令人惊讶的是，由这些低比例制成的聚合复合物在电泳过程中几乎没有凝胶延迟。这些结果证明松散包装的HK聚合复合物在体内有效转染肿瘤。
Histidine-containing polymers show promise in their transport of nucleic acidsin vitroandin vivo. In addition to the pH-buffering histidine component, the polymer often contains a protonated component at physiological pH, such as lysine. These polyplexes usually accumulate in the tumor by enhanced permeability and retention, which has proved disappointing in clinical trials. We presently compare two histidine-lysine (HK) peptide polyplexes for their neuropilin-1-mediated transport of plasmidsin vivo. While the polymerized HK (H2KC-48) polyplex was markedly better than the monomeric HK (H2K) polyplexin vitro,both HK polyplexes were effective in transfecting tumor xenografts over a wide range of peptide and plasmid ratios. Nevertheless, polyplexes of low peptide/DNA ratios gave higher tumor transfection and specificity than those of higher ratios. Surprisingly, there was minimal to no gel retardation of polyplexes made from these low ratios during electrophoresis. These results demonstrate that loosely packed HK polyplexes effectively transfected tumorsin vivo.