Construction And Application Of C(RGDfC)-PEG-PCL-DOX&ce6 Targeted Nano Drug Delivery System

Tumors are one of the most serious diseases that threaten human health,and the prevalence of cancer is increasing year by year.It is imperative to study ways to effectively treat tumors.Traditional methods of cancer treatment are also currently the most commonly used methods of surgical resection,chemotherapy and radiation therapy.However,they all have different deficiencies.For example,although surgical resection can alleviate the pain of patients,it can also remove some normal tissues while removing tumors,and it is difficult to cure tumors.Chemotherapy can effectively treat tumors,but chemotherapy drugs are generally used.Insoluble in water,poor biocompatibility,short cycle time in the body,and does not have the ability to specifically recognize tumor cells,causing damage to both tumor cells and normal tissues.As the treatment cycle prolongs,the drug resistance of tumors also occurs.It will affect the therapeutic effect;radiotherapy has a wide range of treatment,but the radioactive elements cause large radiation to the organism,which seriously damages the health of the organism.Functionalized polyethylene glycol-polycaprolactone(PEG-PCL)has good biocompatibility and biodegradability,and has been widely used in nanocarriers,drug delivery and drug delivery due to its unique physicochemical properties.The application of PEG-PCL has broad application prospects in cancer therapy.In this paper,polyethylene glycol-polycaprolactone(PEG-PCL)was used as a nanocarrier,and an addition reaction was carried out by a maleimide group at one end of polyethylene glycol and a side chain thiol group targeting a cyclic peptide c(RGDfiC).Synthesis of drug-loaded precursor c(RGDfC)-PEG-PCL with the function of targeting tumor vascular endothelial cell integrin av(3;chemotherapeutic drug doxorubicin(DOX)and photosensitizer chlorin(ce6)by physical embedding The solution was loaded into the hydrophobic cavity of c(RGDfC)-PEG-PCL to form a c(RGDfC)-PEG-PCL-DOX&ce6 targeted nano drug delivery system.The material was characterized by ultraviolet-visible spectrophotometer,nuclear magnetic,transmission electron microscopy and particle size;the drug release of the material was studied by simulating the temperature and pH environment of the human body and the tumor site in vitro;the toxicity of the material to the cells was studied by in vitro cell experiments.And the ability of tumor cells to take up materials.The main research results are as follows:(1)The solid phase synthesis conditions of the linear peptide RGDfC were optimized.The optimal conditions were activated amino acid 20 min,DIC/HOBT as condensation reagent,molar ratio of 1:3 and substitution degree of 0.5;optimized cyclic peptide The liquid phase synthesis conditions of c(RGDfC)are preferably carried out at a reaction temperature of 0? and using PyBOP/HOBt/DIEA as a condensation reagent.The purity of the finally synthesized targeting cyclic peptide c(RGDfC)was 95.187%,and the yield was 2.84%.(2)The synthesis conditions of c(RGDfC)and PEG-PCL were optimized.The optimum conditions were reaction time of 24 h,pH value of 7.5-8.0,temperature of 25 ?,addition of basic catalyst DIEA,and use of DMF as reaction solvent.The final synthesis rate of c(RGDfC)-PEG-PCL was 72.6%.(3)The characterization results showed that the hydrated particle size of c(RGDfC)-PEG-PCL-DOX&ce6 was 228 nm;the drug loading of DOX in c(RGDfC)-PEG-PCL-DOX&ce6 was 26.0%,and the drug loading of ce6 was 9.9.%;in vitro release experiments show that the drug release rate is faster in the acidic environment of the tumor,and the release of the drug can be controlled by laser irradiation;in the toxicity test of the material on 4T1 cells,c(RGDfC)-PEG-PCL-DOX&ce6 laser irradiation The group had the greatest effect on the activity of mouse breast cancer cells(4T1).When the concentration was 10?g/ml,the activity of 4T1 was only 18.42%.In the toxicity test of human umbilical vein endothelial cells(HUVEC),The effect of c(RGDfC)-PEG-PCL-DOX&ce6 targeted nano drug delivery system on human umbilical vein endothelial cell activity was smaller than that of free drug DOX&ce6,indicating that the drug DOX&ce6 after encapsulation reduced the lethality to human normal cells.In the cell uptake assay,the c(RGDfC)-PEG-PCL-DOX&ce6 targeted nano drug delivery system is rapidly ingested by tumor tissue.In summary,this topic synthesizes a targeted nano drug delivery system capable of co-administering drugs.This nano drug delivery system with precise targeting function of tumor cells provides a new idea for the precise treatment of tumors.