Layered Double Hydroxide Nanosheet Combined With Tea Polyphenol To Enhance Chemotherapy/chemodynamic Therapy Of Tumors

Chemodynamic therapy(CDT)is an emerging cancer therapy strategy that has received increasing attention due to its unique tumor microenvironment(TME)responsiveness and minimal adverse side effects.As a conventional cancer treatment,chemotherapy has remarkable therapeutic effect but obvious toxic and side effects.But the therapeutic effect of treatment alone is always limited,which is difficult to eradicate the tumor and inhibit metastasis.Therefore,how to design a nanoplatform with superior to achieve chemo-chemodynamic therapy has become a hot topic.In this study,Fe-doped layered double hydroxide(LDH)nanosheets were synthesized via the hydrothermal method to load the anticancer drug epigallocatechin-3-O-gallate(EGCG),and then LDH-EGCG-HA nanoplatform was constructed by modified hyaluronic acid(HA)for specifically target tumor cells overexpressing CD44 receptors and cooperative chemo-chemodynamic therapy.Their structure and physicochemical property were characterized by scanning electron microscopy(SEM),transmission electron microscope(TEM),UV-vis spectrum,X-ray diffraction(XRD)and dynamic light scattering(DLS).The experimental results showed that LDH-EGCG-HA nanomaterials have good colloid stability,high drug loading rate(88%)and sensitive p H-responsive drug release features.In vitro experiments showed that the LDH-EGCG-HA nanoplatform had excellent cytocompatibility to fibrosarcoma cells L929 normal cells,and could specifically target tumor cells overexpressing CD44 receptors,quickly release iron ions and EGCG at TME,and efficiently generate toxic hydroxyl radicals with the acceleration of Fe³⁺/Fe²⁺cycling in Fenton reaction by EGCG.Western blot experiment showed that the cooperative cancer cell inhibition effect through chemo-chemodynamic therapy was achieved by the significant upregulation of caspase-3 and p53 expression to induce the cell apoptosis,and the deactivation of x CT and GPX-4 to inhibit GSH synthesis and reduce lipid peroxides for reinforced ferroptosis.In vivo experiments results demonstrated that the LDH-EGCG-HA obtained have superior biocompatibility and inhibit the growth of tumor effectively by the specific accumulation and the synergistic chemo-chemodynamic therapy.Therefore,LDH nanoplatform may serves as a good starting point for further development of high-performance multimodal antitumor nanomaterials.