Medical implants serve as pivotal therapeutic interventions for cardiovascular diseases. Nevertheless, challenges including endothelial injury, excessive smooth muscle cell migration, and inflammatory responses associated with implantation hinder their long-term adoption in vivo. In this work, a versatile coating of cardiovascular implants was constructed by the remarkable adhesive properties of dopamine and the precision and efficiency of click chemistry. The functional coating was obtained through programmed assembly of heparin, miR-155 inhibitor, and endothelial cell affinity peptide. Cellular experiments have demonstrated that this coating could modulate macrophage phenotype through anti-miR155 inhibitors, thereby inhibiting the release of inflammatory factors and improving the inflammatory environment on the surface. Furthermore, this coating could also promote the adhesion and proliferation of endothelial cells while inhibiting the excessive proliferation of smooth muscle cells, thereby ensuring the endothelialization of the implant surface. Additionally, animal experiments have revealed the coating's exceptional anticoagulant properties, significantly reducing the formation of thrombus. With its simple and efficient preparation process and excellent performance, this coating emerges as a promising candidate for promoting early endothelialization and improving the performance of cardiovascular implants.
Qingyan Zhang,Ying Huang,Ruoxi Yang,Junmei Mu,Zhanwei Zhou,Minjie Sun
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 in vitro and in vivo. 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.