NMPA Key Laboratory for Research and Evaluation of Pharmaceutical Preparations and Excipients, State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, P. R. China.
Biomater Sci. 2022 Jun 28;10(13):3637-3646. doi: 10.1039/d1bm02022f.
Despite the great progress in the control of primary tumor growth, metastasis remains the major challenge of breast cancer therapy in clinics, which is highly related to the upregulation of reactive oxygen species (ROS) and overexpression of its relevant pro-survival miR-155 gene. Therefore, we fabricated a poly-antioxidant (FTP) to deliver anti-miR-155 for synergistic treatment of metastatic breast cancer by ROS scavenging and miR-155 inhibition. FTP was synthesized by the polymerization of fluorated-polyethyleneimine (FPEI) and antioxidants (TEMPOL), using a glutathione (GSH) responsive linker for controlled drug release. Notably, the poly-drug strategy could not only promote the tumoral accumulation of small molecular antioxidants but also enhance the transfection efficiency of anti-miR-155 owing to the hydrophobic property of TEMPOL. After synergistic treatment, the NF-κB pathway was significantly blocked, thereby generating strong anti-metastatic ability both and . The poly-antioxidant could be a new type of nanoplatform for highly efficient and safe miRNA delivery, which also provides a promising strategy for the synergistic treatment of metastatic breast cancer.
尽管在控制原发性肿瘤生长方面取得了巨大进展，但转移仍然是乳腺癌临床治疗的主要挑战，这与活性氧 (ROS) 的上调和相关的促生存 miR-155 基因过表达高度相关。因此，我们通过 ROS 清除和 miR-155 抑制，设计了一种多抗氧化剂 (FTP) 来递送抗 miR-155，以协同治疗转移性乳腺癌。FTP 通过氟化聚乙烯亚胺 (FPEI) 和抗氧化剂 (TEMPOL) 的聚合，使用谷胱甘肽 (GSH) 响应性连接子进行药物控制释放来合成。值得注意的是，由于 TEMPOL 的疏水性，多药策略不仅可以促进小分子抗氧化剂在肿瘤中的积累，还可以提高抗 miR-155 的转染效率。协同治疗后，NF-κB 途径被显著阻断，从而在体内和体外都产生了强大的抗转移能力。多抗氧化剂可为高效和安全的 miRNA 递送提供一种新型纳米平台，也为协同治疗转移性乳腺癌提供了一种有前途的策略。
