The Preparation And Biomedical Properties Of PH-sensitive Nanocarrier

Cancer is one of the main causes of death.Currently,in addition to surgical intervention,the treatment of cancer depends on radiotherapy and chemotherapy.However,these treatments also kill normal cells while killing tumor cells,thereby causing toxic side effects to patients.Through the rational design of the nano drug carrier structure,it can overcome multiple biological barriers and selectively target tumor cells,which has important significance for the treatment of cancer.Since tumor cells mainly provide energy through anaerobic respiration,the pH value of their extracellular environment(pHe)is generally lower than that of normal tissues.In view of the above characteristics of tumor pHe,a three-arm structure polymer nano drug carrier with pH responsiveness was designed and synthesized in this thesis.The efficient enrichment of the drug in the tumor tissue was achieved by responding to the weak acidity of the tumor microenvironment.First,a bifunctional macromolecular chain transfer agent containing PEG5K was synthesized,a monomer C7A-MA and anticancer prodrug HEMA-SN38 were introduced by atom transfer radical polymerization(ATRP)and reversible addition-fragmentation chain transfer polymerization(RAFT),respectively.The polymer self-assembles in an aqueous solution to form a micelle with an amphiphilic core-shell structure.After research,the particle size of this nanoparticle is about 50 nm.When the pH of the environment changes from 7.4 to 6.5,the micelle changes from electrically neutral to positively charged on the surface.The surface of the cancer cell is negatively charged and can be electrostatically adsorbed,so it will promote the uptake of nanoparticles by cancer cells.Then,the drug carrier was used to embed the gambogic acid,and the biological function of the cell was studied.The effects of the drug carrier on cytotoxicity,cell uptake,apoptosis and cell cycle were examined,indicating that the drug carrier has a good inhibitory effect on human breast cancer cell MCF-7 and mouse breast cancer cell4T1.