Thymosin α1 (Tα1), a hormone containing 28 amino acids, has been approved in several cancer therapies, but the lack of tumor-targeting hinders its full use in tumor treatment. We designed a new peptide by connecting Tα1 and RGDR, generating a product, Tα1-RGDR, where RGDR is located in the C-end with both tumor-homing and cell internalizing properties (C-end rule peptides, a consensus R/KXXR/K motif). This work aimed to study the antitumor and immunological activities of Tα1-RGDR, and its differences compared with the wild-type Tα1. The antitumor and immunological activities of Tα1-RGDR were measured using the B16F10 tumor and immunologic suppression models. Tα1-RGDR treatment led to significant inhibition of tumor growth at a dose at which Tα1 showed a slight effect in the B16F10 tumor growth model. In the immunologic suppression model, Tα1-RGDR shared almost equivalent immunomodulatory effect with Tα1. These results demonstrated the better therapeutic effects after treatment with Tα1-RGDR compared with Tα1. Moreover, both Tα1-RGDR and Tα1 shared a helical conformation in the presence of trifluoroethanol based on CD spectroscopy. Our dock information of Tα1-RGDR when combined with integrin αvβ3 or neuropilin-1 further confirmed previous experimental results. All these findings suggest that Tα1-RGDR might be a useful therapy for tumors by overcoming its wild type limitation of tumor homing.

胸腺素α1（Tα1）是一种包含28个氨基酸的激素，已在多种癌症治疗方法中得到批准，但缺乏靶向肿瘤的药物阻碍了其在肿瘤治疗中的全面应用。我们通过连接Tα1和RGDR设计了一种新的肽，生成了一个产物Tα1-RGDR，其中RGDR位于C端，具有肿瘤归巢和细胞内化特性（C端规则肽，共有R / KXXR / K主题）。这项工作旨在研究Tα1-RGDR的抗肿瘤和免疫活性，以及​​与野生型Tα1的区别。使用B16F10肿瘤和免疫抑制模型测量Tα1-RGDR的抗肿瘤和免疫活性。在B16F10肿瘤生长模型中以Tα1显示轻微作用的剂量下，Tα1-RGDR治疗可导致肿瘤生长的显着抑制。在免疫抑制模型中 Tα1-RGDR与Tα1具有几乎相同的免疫调节作用。这些结果表明，与Tα1相比，用Tα1-RGDR治疗后具有更好的治疗效果。此外，基于CD光谱法，在三氟乙醇存在下，Tα1-RGDR和Tα1均共享螺旋构象。当我们将Tα1-RGDR与整联蛋白αvβ3或Neuropilin-1结合时，其对接信息进一步证实了先前的实验结果。所有这些发现表明，Tα1-RGDR通过克服其野生型的肿瘤归巢限制，可能是一种有用的肿瘤治疗方法。当我们将Tα1-RGDR与整联蛋白αvβ3或Neuropilin-1结合时，其对接信息进一步证实了先前的实验结果。所有这些发现表明，Tα1-RGDR通过克服其野生型的肿瘤归巢限制，可能是一种有用的肿瘤治疗方法。当我们将Tα1-RGDR与整联蛋白αvβ3或Neuropilin-1结合时，其对接信息进一步证实了先前的实验结果。所有这些发现表明，Tα1-RGDR通过克服其野生型的肿瘤归巢限制，可能是一种有用的肿瘤治疗方法。