Construction Of Nanoreactors Based On Biofunctionalized Metal-organic Framework Materials For Cancer Diagnosis And Treatment Researc

With the development of nanotechnology,functional nanomaterials play an increasingly important role in the field of biological science.Metal-organic frameworks(MOFs)are a new type of porous nanomaterials.Owing to controllable size,tunable structure,and good biocompatibility,MOFs show great potential in the biomedical field.In this paper,a novel MOFs-based nanoreactor has been constructed,which can trigger the controlled release of drugs under the stimulation of the slightly acidic tumor microenvironment(TME),and further achieves the synergistic starvation/metal-ion therapy for cancer,which provides novel research ideas and strategies for the construction of multifunctional therapy platform and the development of nanotechnology in the biomedical field.This paper mainly carries out the following two works:1.Construction of p H-responsive multifunctional Ag NCs/GOx@ZIF nanoreactor based on MOFsFirst,the p H-responsive Ag NCs/GOx@ZIF nanoreactor was prepared by encapsulating glucose oxidase(GOx)and silver nanoclusters(Ag NCs)into zeolite imidazole framework-8(ZIF-8)by a "one-pot" method.The Ag NCs/GOx@ZIF nanoreactor exhibits good stability under neutral conditions,but can be disintegrated in the acid condition,leading to a controlled release of the loaded GOx and Ag NCs.In addition,GOx in the Ag NCs/GOx@ZIF nanoreactor specifically catalyzes the oxidation of glucose,and the in situ generated H2O2 oxidize neighboring Ag NCs,achieving cascaded glucose consumption and Ag+ release.The multifunctional nanoreactor has the advantages of simple preparation,rapid stimulus-response,and strong reactivity,which can be further applied in drug delivery and cancer treatment.2.Application of p H-responsive Ag NCs/GOx@ZIF nanoreactor for synergistic starvation/metal-ion therapy of malignant tumorBased on the ability of Ag NCs/GOx@ZIF nanoreactor to respond to p H and initiate cascade reactions,the synergistic therapy effects of the nanoreactor for cancer are further explored in vitro and in vivo.Once the Ag NCs/GOx@ZIF nanoreactor is ingested by tumor cells,the decomposition of ZIF-8 can be triggered by the mildly acid tumor microenvironment(TME)and the internal GOx and Ag NCs are released.GOx can rapidly deplete intracellular glucose and molecular oxygen to hinder the tumor metabolic pathways.Meanwhile,the released Ag NCs can be oxidized by H2O2 produced by glucose oxidation to generate cytotoxic Ag+ for the enhanced metal ion therapy,realizing the combinational cancer therapy.Significantly,both in vitro and in vivo results validate that the p H-responsive Ag NCs/GOx@ZIF nanoreactor can specifically induce tumor cell apoptosis and achieving precise treatment of malignant tumors.Therefore,the p H-responsive Ag NCs/GOx@ZIF nanoreactor has great potential in the development of nanomedicine.