Folate-mediated magnetic and pH/GSH dual-responsive metal-polymer-coordinated nanocomplexes for joint chemo/chemodynamic anti-breast cancer therapy

Abstract

It is of great significance to develop a drug carrier that effectively targets chemotherapeutic drugs to the tumor site, improves therapeutic efficacy and reduces side effects associated with high-dose medicines. In the present study, an intelligent drug carrier system, FA-β-CD/DOX@Cu2+@GA@Fe3O4, was synthesized by skillfully introducing metal ions as a bridge base. The performance of the prepared FA-β-CD@Cu2+@GA@Fe3O4 metal-polymer-coordinated nanocomplexes were determined by UV-visible spectroscopy, NMR, FT-IR, XPS, VSM, DLS, and TEM analysis. The data showed that these nanocomplexes had good pH/GSH-responsive drug release behavior, and enabled enhanced magnetic and folic acid-mediated tumor cell targeting. Moreover, the toxicity effects of the FA-β-CD/DOX@Cu2+@GA@Fe3O4 on 3T3 cells and 4T1 cells were measured by the MTT method, and it was found that it displayed low cytotoxicity against 3T3 cells and had a stronger effect on killing 4T1 cells than DOX alone. The results also showed that the Cu2+-based coordination polymers had a significant ability to deplete GSH and generate ROS. It could be concluded that the introduction of Cu2+ not only facilitated the assembly of nanocomplexes, but also successfully enhanced the anti-tumor effect, making FA-β-CD@Cu2+@GA@Fe3O4 a potential nanoplatform for effectively mediating combined chemotherapy and chemokinetic therapy for tumors. All these characteristics verified the great potential of FA-β-CD/DOX@Cu2+@GA@Fe3O4 in multipurpose smart drug delivery systems, accelerating the application range of metal-polymer-coordinated nanocomplexes in biomedical fields.