Construction Of Magnetic Nanometer Drug Delivery System And Research Of Antitumor Activity

As a malignant disease,tumor is a serious threat to human health.The incidence of cancer remains high,and chemotherapy is still the most extensive choice in clinical cancer treatment.Chemotherapy is still the most extensive choice in clinical cancer treatment.Traditional anticancer drugs cannot distinguish between cancer cells and healthy cells,will also cause certain damage and side effects to normal cells,it is urgent to develop a new anticancer drug carrier that can target cancer cells.As a new type of nanomaterial,magnetic nanoparticles have high photothermal stability,strong catalytic activity,stable chemical properties and specific magnetic response characteristics.Therefore,magnetic nanomaterials can be used in magnetic separation,cell sorting,magnetic responsive drug carriers,magnetic targeted thermotherapy and magnetic resonance contrast agent.Large-scale drug delivery systems,such as drug-polymer conjugates,micelles,liposomes,dendrimers,and inorganic nanoparticles,have been developed in existing technology to utilize their strong permeability and retention（passive targeting）for specific delivery.Mesoporous nanoparticles have attracted great attention in the development of these"smart"drug delivery systems.They have become powerful drug delivery nanocarriers because of their unique functions such as adjustable particle size and pore size,controllable drug release mode,high specific surface area and good biocompatibility.Specifically,in these drug delivery systems,the plugging substances on the mesoporous surface can be controlled released by various stimuli,such as the change of redox state,p H,static electricity,enzyme activity,light irradiation,magnetic response and electric field.From the above research background,we have successfully constructed a series of drug delivery systems based on magnetic nanoparticles,loading chemotherapy drug donamycin（DNM）by modifying groups on the surface of mesoporous,and blocking it with endogenous stimuli responsive inorganic substances,so that it has dual targeting function of magnetic/endogenous substances,and evaluated the drug delivery system in vitro and cytological level The antitumor mechanisms of the complex include targeting,sensitive delivery efficiency,cytotoxicity,migration and apoptosis.This paper is divided into three chapters.The specific research contents are as follows:（a）To construct the DNM@MMSN-SS-Zn O delivery system and test its antitumor activity in vitro.The drug-loading system is based on magnetic nanoparticles wrapped by mesoporous silica nanoparticles to form a core-shell nanocomposite.The nanoparticle channels modify disulfide bonds and load anti-tumor drugs,and then the nanoparticle channels are connected by amide bonds to Zn O-COOH for blocking and formation.After being drug delivery carrier system reach the tumor area,disulfide bond is tumor area high expression of glutathione（GSH）fracture,oxidation and sealing material Zn O QD-COOH generated under the condition of acid dissolved in the tumor area Zn²⁺,ammonia condensation generated schiff’s base fracture under acid condition,form a"dual switch"response,remove plugging effect and release drugs,the generated Zn²⁺can lead to reactive oxygen species（ROS）generation,cause inflammation and cell death,and release of drug DNM synergy play a role of cytotoxicity.（b）To construct the delivery system of MMZr@Bi₂O₃-DNM and study its anti-tumor activity in vitro.This chapter was synthesized with superparamagnetism oxide as the nucleus,hollow zirconium dioxide as shell,bismuth oxide nanoparticles for sealing load anti-cancer drugs,drug（DNM）drug system,when the drug system influenced by tumor acidic environment,load of antitumor drug release,and bismuth oxide dissolution of bi³⁺produce cytotoxic create synergies and mutual kill tumor cells.（c）Build the delivery system of MMZr@Mn O₂-DNM and test its anti-tumor activity in vitro.Using the characteristics of high GSH concentration in the tumor microenvironment,superparamagnetic Fe₃O₄coated with mesoporous zirconia blocked by Mn O₂was designed.When the nano-complex entered the tumor cells under the action of external magnetic field,Mn O₂was reduced to manganese ions,and the loaded anti-tumor drugs were released to cause cell death.