Improving NK1R-targeted gene delivery of stearyl-antimicrobial peptide CAMEL by conjugating it with substance P.
Improving NK1R-targeted gene delivery of stearyl-antimicrobial peptide CAMEL by conjugating it with substance P.
复制标题
通过将硬脂酰抗菌肽 CAMEL 与 P 物质结合来改善 NK1R 靶向基因递送。
DOI：
10.1016/j.bmcl.2020.127353
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发表时间：
2020-08
影响因子：
2.7
通讯作者：
Zhang Wei
中科院分区：
文献类型：
--
作者：
Song Jingjing;Huang Sujie;Ma Panpan;Zhang Bao;Jia Bo;Zhang Wei
特异性是阻碍非病毒载体应用于癌症基因治疗的关键条件。在之前的研究中，我们利用抗菌肽 CAMEL 的 N 末端硬脂基化，开发了一种高效的基因载体硬脂基-CAMEL。 P 物质 (SP) 是一种 11 个残基的神经肽，与在许多癌细胞系中表达的神经激肽-1 受体 (NK1R) 结合后迅速进入细胞。本研究通过将SP与硬脂基-CAMEL的C端缀合，构建了NK1R靶向基因载体硬脂基-CMSP。我们的结果表明，与硬脂基-CAMEL 相比，硬脂基-CMSP 对表达 NK1R 的细胞表现出显着的转染特异性。因此，硬脂酰-CMSP/p53质粒复合物对HEK293-NK1R细胞的抗增殖活性明显高于对HEK293细胞的抗增殖活性，而硬脂酰-CAMEL/p53质粒复合物在抗增殖活性中没有表现出这种特异性。因此，NK1R靶向配体SP的缀合是构建有效的癌症靶向非病毒基因载体的简单而成功的策略。
Specificity is a crucial condition that hampers the application of non-viral vectors for cancer gene therapy. In a previous study, we developed an efficient gene vector, stearyl-CAMEL, usingN-terminal stearylation of the antimicrobial peptide CAMEL. Substance P (SP), an 11-residue neuropeptide, rapidly enters cells after binding to the neurokinin-1 receptor (NK1R), which is expressed in many cancer cell lines. In this study, the NK1R-targeted gene vector stearyl-CMSP was constructed by conjugating SP to the C-terminus of stearyl-CAMEL. Our results indicated that stearyl-CMSP displayed significant transfection specificity for NK1R-expressing cells compared with that shown by stearyl-CAMEL. Accordingly, the stearyl-CMSP/p53 plasmid complexes had significantly higher antiproliferative activity against HEK293-NK1R cells than they did against HEK293 cells, while the stearyl-CAMEL/p53 plasmid complexes did not show this specificity in antiproliferative activity. Consequently, conjugation of the NK1R-targeted ligand SP is a simple and successful strategy to construct efficient cancer-targeted non-viral gene vectors.
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DOI：
10.1016/j.jconrel.2013.08.300
发表时间：
2013-12-28
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
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通讯作者：
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影响因子：
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影响因子：
4
作者：
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DOI：
10.1007/s00249-011-0682-7
发表时间：
2011-04-01
影响因子：
2
作者：
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通讯作者：
Neundorf, Ines
影响因子：
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通讯作者：
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