A PH-responsive Platform Combining Chemodynamic Therapy With Limotherapy For Simultaneous Bioimaging And Synergistic Cancer Therapy

Objective Nowadays,the diagnosis and treatment of cancer is one of the hot topics in medical research.Nowadays,chemical dynamic therapy?CDT?is widely used in cancer treatment,which is expected to replace the traditional anticancer drug treatment.Generally speaking,CDT needs to be combined with additional treatment methods to achieve the best cancer treatment effect.Here,we hope to develop a multi-functional treatment and diagnosis platform combining CDT,starvation therapy and tumor specific MRI through the integration of nano selenium,manganese carbonate and iron oxide nanoparticles.Methods MCDION could be synthesized by solvent-thermal decomposition using iron acetylacetonateand manganese acetylacetonateas precursors and polyethyleneimine?PEI?as a surfactant.Subsequently,PEI was used to further modify MCDION for obtaining a highly positive charge,making nano-selenium with negative charge effectively coated on MCDION to form MCDION-Se.The physical and chemical properties of the synthetic materials were studied by electron microscopy,thermogravimetry and inductively coupled plasma mass spectrometry.The biocompatibility of the materials was studied by CCK-8 cell experiment.Cell uptake and ROS effect were studied by flow cytometry and laser confocal.BALB/C nude mice were used to establish subcutaneous tumor bearing model to study the anticancer effect and distribution of nano diagnosis and treatment system in vivo.Results The p H responsive multifunctional agent MCDION-Se can release a large number of Mn²⁺ions after entering the acidic environment of tumor,which endows MCDION-Se with the ability of MR imaging of tumor tissue.In addition,the released Mn²⁺ions catalyze H2O2 to form toxic·OH in cancer cells through Fenton like reaction,and also inhibit the formation of adenosine triphosphate?ATP?.Based on the reaction between SOD and soars,the content of H2O2 in cancer cells can be increased.H2O2further catalyzes the formation of·OH by Mn²⁺and iron oxide nanoparticles?IONs?,which leads to cancer cell apoptosis.Nano selenium also acts as an ATP inhibitor,blocking the energy demand of cancer cells,further leading to the apoptosis of cancer cells and improving the therapeutic effect of cancer.It was found that the biocompatibility of MCDION to normal somatic cells was good,while the cytotoxic effect of MCDION-Se on tumor cells was concentration dependent.The difference was statistically significant?P<0.05?.Conclusion We have successfully developed a drug-free diagnostic and therapeutic agent?MCDION-SE?for real-time MRI and cooperative tumor therapy.MCDION-Se integrates CDT with starvation therapy and tumor specific MRI systematically.This system can be a good alternative to traditional chemotherapy,and is expected to provide a good application prospect for MRI visualization tumor therapy.The drug-free nano platform combined with MRI and synergistic effect is expected to be a good candidate for the development of the next generation of tumor drugs.