Study Of Drug-delivery System Based On Nanocarriers Of Molybdenum Disulfide And Silica In The Treatment Of Osteoarthritis And Cancer

Nanomedicine is the science of using engineered nanomaterials to achieve a medical effect?such as disease diagnosis,treatment,or treatment?.Among them,pharmaceutical preparations are one of the most extensive areas of nanomedicine research,which inject nano-injections into the human body for disease diagnosis or treatment.The traditional nanoparticulate drug delivery systems?NDDSs?is designed to overcome the limitations of traditional drugs such as poor solubility,short half-life of blood and non-targeting,while the rapid development of nanomedicine enables NDDSs to deliver drugs to pathological areas more efficiently through innovative and intelligent design.At present,there are multifunctional NDDSs designed to combine biomedical imaging with innovative disease treatment functions,which can achieve more effective disease treatment through imaging guided therapy and detection of metabolism.This also provides new ideas for the treatment of various diseases such as arthritis and Alzheimer's disease in addition to cancer.Nanoparticles?NPs?are important components of NDDSs,including soft NPs?such as liposomes?and hard NPs?such as gold NPs?.Inorganic NPs are diverse in variety and their unique physicochemical properties make them widely used in the construction of NDDSs for disease treatment,diagnosis or diagnosis.Among them,two-dimensional nanomaterials are the thinnest materials in known materials,have the largest surface area to volume ratio,and have great potential for drug delivery and release.Mesoporous nanomaterials are widely used as transport carriers for various molecular weight therapeutic agents with their large specific surface area and pore volume.?However,physiological barriers in organisms affect the bioavailability of NDDSs,while the safety of inorganic NDDSs limits their further clinical transformation.A detailed understanding of the interaction between NDDSs and organisms,precise control of the synthesis of NDDSs,comprehensive evaluation of the biosafety of NDDSs has important guiding significance for the realization of its clinical transformation.Based on the above research background,this paper designed and synthesized two nano drug delivery systems:a near-infrared photoresponsive drug controlled release system based on molybdenum disulfide nanosheets and a tumor microenvironment response drug controlled release system based on mesoporous silica.And their therapeutic effects on osteoarthritis and cancer and their therapeutic mechanisms were also stdied respectively.The full text is divided into three chapters.The first chapter:Introduction,introduces the application of NDDSs based on inorganic NPs in the treatment,diagnosis and diagnosis of diseases.Mainly from the four aspects of inorganic NDDSs in treatment in vivo,biomedical imaging,disease diagnosis and treatment,and the challenges faced.The application of inorganic NDDSs in disease treatment is highlighted.The second chapter:Molybdenum disulfide nanosheets were synthesized by simple mechanical exfoliation.After the biocompatible chitosan was chemically modified,the anti-inflammatory drug dexamethasone was loaded,synthesizing a intra-articular drug delivery nanosystem MoS₂@CS@Dex?MCD?capable of responding to near-infrared light and controlling drug release.In our studies of photothermal properties and drug release behavior in vitro,it turned out that MCD has good photothermal conversion ability and can respond to near-infrared light to release drugs.Next,in cell experiments related to inflammatory cell models,MCD can down-regulate inflammatory factors in inflammatory cells and reduce their effects on chondrocyte metabolism.Finally,in the study of the therapeutic effect of osteoarthritis model mice,in mice and prolong the residence time of the drug in the joint cavity.it was found that MCD still has the ability of photothermal conversion and can prolong the retention time of the drug in the articular cavity.Meanwhile,it was found that MCD treatment was superior to traditional drugs and had no toxic side effects.It shows that MCD has great potential for the treatment of osteoarthritis.The third chapter:After the mesoporous silica was synthesized via"template method",the phthalocyanine green was loaded.After that,the MnO₂ shell was grown in situ and PEG was modified,synthesizing the NDDSs MS-ICG@MnO₂@PEG?MIMP?that can respond to and regulate the tumor microenvironment and treat breast cancer by enhanced photodynamic therapy?PDT?and chemical dynamic therapy?CDT?.First,in an in vitro performance evaluation experiment,MIMP can consume GSH and cooperate with CDT/enhanced PDT to produce ROS.Second,at the cellular level,MIMP can alter intracellular redox levels,upregulate intracellular ROS,and induce apoptosis in 4T1 cells by disrupting mitochondrial oxidative stress.In the study of in vivo tumor models,it turned out that MIMP can inhibit tumor growth and inhibit lymphatic metastasis of cancer cells by improving tumor microenvironment and treatment,and has no toxic side effects on major internal organs in the body.The experimental results demonstrate that MIMP has the potential to clinically transform to treat breast cancer.