Construction Of Molybdenum Disulfide Nano Drug Delivery System And Its Application In Combined Photothermal-chemical Therapy Of Tumors

Due to the increasing incidence of tumor,the research of antitumor therapy has become one of the hotspots in the field of biomedicine.Traditional and single tumor treatment has great disadvantages,and can not effectively cure tumor patients.In recent years,with the rapid and vigorous development of nano materials,new tumor treatment methods such as photothermal therapy have been widely used in the field of tumor treatment,especially through the use of two or more combined treatment methods,the cure efficiency of tumor patients can be improved.In photothermal therapy,molybdenum disulfide（MoS₂）has become a potential drug delivery carrier and photothermal therapeutic agent because of its low cost,high biological stability and good photothermal conversion ability in the near infrared region.Therefore,based on MoS₂ nanoparticles,two nano drug delivery systems were constructed and used in antitumor therapy.The main research contents are as follows:（1）Taking MoS₂ nanoparticles as the skeleton,manganese dioxide（Mn O₂）with tumor microenvironment response was coated on its surface by liquid deposition to form a mesoporous core-shell structure,and then loaded with antitumor drug DOX.Then,amino polyethylene glycol（m PEG-NH₂）was modified on the surface of the MoS₂@DOX/Mn O₂ by cationic polymer to improve water solubility and stability,finally preparation the MoS₂@DOX/Mn O₂-PEG（MDMP）nano drug loaded particles.TEM,SEM,UV-Vis and FTIR were used for characterization.The results showed that MDMP nanoparticles with an average particle size of about 236 nm were successfully synthesized,the photothermal conversion efficiency was 33.7%,and the drug loading rate and release rate of DOX were 13%and 65%respectively.In vitro cytotoxicity experiment,when the concentration of MDMP is 200μg·m L^-1,the inhibition rate of MCF-7 cells treated by MDMP+NIR was 89.7%.In the study of antitumor activity in vivo,after 14 days of treatment,the tumor weight of mice in blank and MDMP groups were 0.1878 g and 0.0703 g respectively,while the tumor weight of mice in MDMP+NIR group was 0.008 g,indicating that combination therapy of MDMP+NIR can effectively inhibit the growth of tumor tissue and improve the survival rate of mice.MDMP nano drug loaded particles show excellent antitumor effect in tumor photothermal-chemical combination therapy,which provides a theoretical basis for the design of the same type of nano drug loaded system.（2）Taking MoS₂ as the basic structure,amino polyethylene glycol amino（m PEG-2NH₂）was adsorbed on its surface by electrostatic adsorption,and then triphenylphosphine（TPP）targeting mitochondria and lornidamine（LND）destroying mitochondrial structure,were loaded by amide bond,finally preparation the MoS₂@PEG-TPP/LND（MPTL）nano drug loaded particles.SEM,UV-Vis and FTIR were used for characterization and the results showed that the MPTL with a diameter of about 208 nm were successfully synthesized,and the drug loading rate of LND was 17.5%,the photothermal conversion efficiency of the nanoparticles is 45%,which is about 11.3%higher than that of MDMP.In the study of antitumor activity in vitro,when the concentration of MPTL is 200μg·m L^-1,the inhibition rate of MPTL+NIR on HGC-27 cells was80%,and the inhibition effect of MPTL on tumor was more obvious than that of simple LND,indicating that the targeting of TPP further improved the utilization of LND.In the study of antitumor activity in vivo,after 14 days of treatment,the tumor weight of mice in MPTL+NIR group was 0.0168 g,which was significantly lower than that of mice in blank（0.1158 g）and MPTL group（0.0377g）,indicating that combination therapy of MPTL+NIR can effectively inhibit the survival of tumor cells in tumor bearing mice and improve the survival rate of mice.The construction and design of MPTL nano drug loaded particles provide a theoretical basis for the nano application of LND.To sum up,two kinds of nano drug loaded particles were designed in this study.The basic characterization methods proved that the two kinds of nanoparticles were successfully synthesized.The antitumor activities of the two nanoparticles were studied in vivo and in vitro.The results showed that the two nanoparticles had excellent antitumor effects.It can be seen that this study has a certain reference significance for the design of nano drug loading system.