Preparation Of Non-covalently Modified Molybdenum Disulfide Drug Delivery System And Its Application In Cancer Treatment

Cancer is still a major problem endangering human health.With the rapid development of nanoscience,the application of nanomaterials in many fields shows an increasingly important position.Two dimensional nanomaterials have been widely studied in biosensor,imaging,gene and drug delivery,and photothermal therapy due to their high drug loading/gene loading,high photo thermal conversion efficiency and photodynamic properties.Molybdenum disulfide,as a new type of graphene inorganic nano material,has unique structure and physical and chemical properties,especially excellent photothermal conversion ability,which has great potential in the field of cancer treatment.However,the stability of molybdenum disulfide under physiological conditions is very poor,so it needs to be modified to improve its biological application performance.In this study,several kinds of molybdenum disulfide based composite nanomaterials were prepared by adding magnetic nanoparticles to the molybdenum disulfide nanowafers,giving them excellent magnetic properties,and then non covalently modifying them,and characterized by TEM,AFM,FTIR,particle size and zeta potential.The in vitro and in vivo properties of these nanomaterials were studied The results are as follows:（1）Many kinds of mMoS₂ nanocomposites were prepared by functional modification of mMoS₂ on the surface of MoS₂ with noncovalent effect.The nanocomposites were characterized by TEM,AFM,FTIR and magnetic analysis.It was proved that the nanocomposites of mMoS₂-CS/SA and mMoS₂-CS/CMC were successfully prepared.The results show that the two nanocomposites have good dispersion and stability under physiological conditions,reduce the adsorption of non-specific proteins,and show excellent photothermal warming performance.The results of drug loading and release showed that these materials have high loading rate of doxorubicin,the release of doxorubicin from the carrier material shows obvious pH dependence,the release level in acid environment is significantly higher than that in neutral condition,and near-infrared laser can also promote the release of drug from the carrier material.This is conducive to the combination of photothermotherapy and chemotherapy to more effective treatment of tumors,while reducing the body’s side effects.In vitro cell experiments show that the pure nanocomposites have no obvious cytotoxicity to cells,can be effectively absorbed by tumor cells,and have magnetic targeting function;a single chemotherapy or photothermal therapy has certain killing power to tumor cells,but the combined treatment effect of the two methods is more efficient.The temperature of the tumor site can rise up to about 50℃under the near-infrared laser irradiation（1.5W/cm²,5min）,showing a good photothermal effect.（2）MoS₂-Lipid and mMoS₂-Lipid nanocomposites were prepared by modifying the surface of the materials with liposomes,and characterized by TEM,AFM and FTIR.Liposome modification significantly improves the biocompatibility of the nanomaterials,and the nanomaterials have large drug loading,pH dependent DOX release performance,excellent photothermal performance and ideal cell uptake.Therefore,chemotherapy and photothermal therapy are combined to treat tumor.Through the cell experiment in vitro,the pure nanocomposites have no obvious killing effect on the cells,and the effect of chemotherapy combined with photothermal therapy is better than that of single therapy.In vivo experiments show that the two nanocomposites can be effectively accumulated in mouse tumors for photothermal treatment.In vivo pharmacodynamic experiments show that the mMoS₂-Lipid nanocomposite can combine chemotherapy and photothermal therapy to achieve a better therapeutic effect on tumor,and it can be used as a contrast agent of MRI to achieve the combination of treatment and diagnosis of cancer treatment.