Liu Changliang, Duan Hongyang, Zhao Zijian, Li Wenzhe, Ma Lilusi, Fang Xiaocui, Wang Chen, Yang Yanlian
CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Key Laboratory of Biological Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology Beijing 100190 P. R. China
Academy for Advanced Interdisciplinary Studies, Peking University Beijing 100871 China.
RSC Adv. 2018 Nov 30;8(70):39948-39956. doi: 10.1039/c8ra08526a. eCollection 2018 Nov 28.
The metastasis of breast cancer is one of the main factors resulting in the high fatality of patients. Although many antagonists have been developed to inhibit the metastasis of breast cancer, their practical application has been limited because of the poor solubility of many chemotherapeutic drugs in the physiological environment. Herein, a complex of E5 peptide antagonist and acetylated PAMAM G5 (P) has been constructed to enhance the solubility of the peptide antagonist. The E5 peptide antagonist has been designed and it was confirmed that it could specifically bind to CXCR4, which is a chemokine receptor involved in the metastasis of several types of cancers, in our previous work. The results demonstrated that P could significantly increase the solubility of the E5 peptide in the physiological environment, as well as the affinity of the E5 peptide to CXCR4-positive cell lines, and the inhibitory effect of the E5 peptide for cell migration . Meanwhile, the passive lung metastasis model of breast cancer was established and the anti-tumor metastasis of the P-E5 complex was evaluated . The results show that the P-E5 complex demonstrated excellent inhibition for the tumor metastasis at an E5 dosage of 10 and 20 mg kg. These effects indicate a feasible strategy to apply the P-peptide complex in cancer therapies to improve the solubility and bioavailability.
乳腺癌转移是导致患者高死亡率的主要因素之一。尽管已经开发了许多拮抗剂来抑制乳腺癌转移，但由于许多化疗药物在生理环境中的溶解度较差，它们的实际应用受到了限制。在此，构建了E5肽拮抗剂与乙酰化PAMAM G5（P）的复合物以提高肽拮抗剂的溶解度。E5肽拮抗剂已被设计出来，并且在我们之前的工作中证实它可以特异性结合CXCR4，CXCR4是一种参与多种癌症转移的趋化因子受体。结果表明，P可以显著提高E5肽在生理环境中的溶解度，以及E5肽对CXCR4阳性细胞系的亲和力，和E5肽对细胞迁移的抑制作用。同时，建立了乳腺癌的被动肺转移模型并评估了P-E5复合物的抗肿瘤转移作用。结果表明，在E5剂量为10和20 mg/kg时，P-E5复合物对肿瘤转移表现出优异的抑制作用。这些结果表明了一种在癌症治疗中应用P-肽复合物以提高溶解度和生物利用度的可行策略。
