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, using N-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.

特异性是阻碍非病毒载体用于癌症基因治疗的关键条件。在先前的研究中，我们使用N来开发有效的基因载体stearyl-CAMEL抗菌肽CAMEL的末端末端固位。P（SP）是一种11个残基的神经肽，与神经激肽-1受体（NK1R）结合后迅速进入细胞，该受体在许多癌细胞系中都有表达。在这项研究中，通过将SP与硬脂基-CAMEL的C末端缀合，构建了靶向NK1R的基因载体硬脂基-CMSP。我们的结果表明，与硬脂基-CAMEL相比，硬脂基-CMSP对表达NK1R的细胞显示出显着的转染特异性。因此，硬脂基-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，而硬脂基-CAMEL / p53质粒复合物在抗增殖活性中未显示出这种特异性。所以，