Although cell-penetrating peptides (CPPs) has been proven to be efficient transporter for drug delivery, ideal peptide vectors for tumor therapy are still being urgently sought. Peptide antagonists have attracted substantial attention as targeting molecules because of their high tumor accumulation and antitumor activity compared with agonists. SPA, a derivative of substance P, is a potent antagonist that exhibits antitumor activity. Based on the amino acid composition of SPA, we speculate that it can translocate across cell membranes as CPPs do. In this study, our results demonstrated that SPA could enter cells similarly to a CPP. As a vector, SPA could efficiently deliver camptothecin and plasmids into cells. In addition, our results showed that SPA exhibited low toxicity to normal cells and high enzymatic stability. Taken together, our results validated the ability of SPA for efficient drug delivery. More importantly, our study opens a new avenue for designing ideal CPPs based on peptide antagonists.

中文翻译：

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SPA：一种肽拮抗剂，起药物穿透细胞的作用。

尽管已经证明细胞穿透肽（CPPs）是药物递送的有效转运蛋白，但仍在紧急寻求用于肿瘤治疗的理想肽载体。肽拮抗剂作为靶向分子已经引起了广泛的关注，因为它们与激动剂相比具有很高的肿瘤蓄积性和抗肿瘤活性。SPA是P物质的衍生物，是一种具有抗肿瘤活性的有效拮抗剂。根据SPA的氨基酸组成，我们推测它可以像CPP一样跨细胞膜转运。在这项研究中，我们的结果表明SPA可以像CPP一样进入细胞。作为载体，SPA可以有效地将喜树碱和质粒传递到细胞中。另外，我们的结果表明SPA显示出对正常细胞低毒性和高酶稳定性。在一起 我们的结果验证了SPA高效递送药物的能力。更重要的是，我们的研究为基于肽拮抗剂设计理想的CPP开辟了一条新途径。