Study On Antitumor Effect Of The Nanodrug Delivery System Based On Molybdenum Disulfide/Sodium Ascorbate

At present,malignant tumors are still one of the main causes of human death.Traditional cancer therapies:chemotherapy,radiotherapy and surgery have various drawbacks,and many researchers have combined them with safer and more effective methods to achieve synergistic cancer therapy.Chemodynamic therapy（CDT）is a cancer treatment method based on Fenton or Fenton-like reaction.Its principle is to realize selective tumor treatment by using peroxidase to convert high concentrations of H₂O₂into highly cytotoxic hydroxyl radicals（·OH）in situ in a weakly acidic tumor microenvironment.However,the limited efficiency of the Fenton response results in poor CDT treatment.Therefore,various strategies to enhance the internal Fenton response efficiency of tumor are proposed,which can significantly improve the efficiency of tumor treatment.Molybdenum disulfide（MoS₂）nanomaterials,as a new two-dimensional material,have attracted much attention in cancer therapy.Due to its large specific surface area,MoS₂can be used as a drug carrier to effectively load chemotherapy drugs,showing great potential in the delivery of anti-tumor drugs.In addition,MoS₂also has double nanoenzyme activities of peroxidase-like and catalase-like,which can catalyze tumor endogenous H₂O₂to·OH and O₂,respectively.High-dose vitamin C（Vc）has great potential in anti-tumor,with unique tumor-selective H₂O₂generation ability.The principle lies in the automatic oxidation of Vc into ascorbic acid free radicals and H₂O₂through electronic donors in the presence of Fe³⁺in tumor microenvironment.In addition,Vc can also reduce the side effects of chemotherapy drugs.In this study,a nanodrug delivery system was constructed using MoS₂nanoflowers as carrier,loaded with chemotherapy drugs doxorubicin（DOX）and sodium ascorbate（Vc Na）,and coated with homologous tumor cell membrane,for antitumor therapy.The specific research contents are as follows:Firstly,MoS₂nanoflowers were synthesized by hydrothermal method;Then MoS₂was used as the carrier to load DOX and Vc Na successively by electrostatic adsorption to obtain MoS₂-DOX/Vc Na（MDV）nanoparticles;Finally,the homologous tumor cell membrane was modified on the surface of MDV,and the nano-drug carrying system MoS₂-DOX/Vc Na@M（MDV@M）was constructed.Adhesion molecules highly expressed on the homologous tumor cell membranes can make MDV@M target tumor cells through receptor-ligand specific binding.After drugs uptake by tumor cells through endocytosis,DOX and Vc Na are released acid-responsive in tumor cells.DOX is used to inhibit the synthesis of RNA and DNA.Vc Na has the same effect as Vc,and can be oxidized to produce H₂O₂.Under the catalysis of MoS₂peroxidases,it can enhance the CDT.The O₂produced by the catalysis of MoS₂catalases can also be used for the oxidation of Vc to produce H₂O₂.In addition,dehydroascorbic acid（DHA）,as the oxidative form of Vc,can consume the highly expressed glutathione（GSH）in tumor cells and enhance oxidative stress,which itself is reduced to Vc cycling,meanwhile,Vc also reduces the side effects of chemotherapy.The final treatment group MDV@M demonstrated excellent antitumor effects both in vivo and in vitro experiments.In summary,this design proposes a synergistic treatment strategy of low toxicity chemotherapy to enhance the antitumor effect.