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

AbstractAbstractIt 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.HighlightsAn intelligent drug carrier system FA-β-CD/DOX@Cu2+@GA@Fe3O4 was synthesized by skillfully introducing metal ions as bridge base.Magnetic and receptor-targeting delivery of doxorubicin.It can induce the specific release of therapeutic agents through pH/GSH stimulation.Achieving an efficient tumor-specific chemotherapy/CDT therapy.Keywords: β-Cyclodextrinstargeted deliverydoxorubicincontrolled release AcknowledgmentWe would like to thank Analysis and Testing Center of Southwest Jiaotong University for the confocal microscopy images.Disclosure statementThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article.Additional informationFundingThis work was supported by the National Natural Science Foundation of China (22174117), Basic Research Program of Sichuan Province (2021YJ012), and Fundamental Research Funds for the Central Universities (2682020ZT86 and 2682022ZTPY030).