Construction Of PH-responsive Molybdenum Disulfide Nanoparticles Loaded With Anti-metabolic Drugs And Their Anti-tumor Research

The traditional treatment of tumors has problems such as poor efficacy and easy metastasis and recurrence.As a new treatment method,photothermal therapy has the advantages of real-time and high pertinence,and has been widely used in tumor treatment.The key to photothermal therapy lies in the selection of photothermal agents.Molybdenum disulfide（MoS₂）has become a potential photothermal agent due to its low cost,high biological stability and good photothermal conversion ability in the near-infrared region.In recent years,with the in-depth study of liver cancer,microenvironment-responsive nanomaterials designed for the characteristics of tumor microenvironment（such as low p H,high GSH content）have been widely used.Therefore,in this study,MoS₂nanoparticles were used as carriers,and ZIF-90 was coated on the surface by in-situ growth method to construct two microenvironment-responsive nano-drug delivery systems for the treatment of liver cancer.The main research contents are as follows（1）With MoS₂ nanoparticles as the core,ZIF-90 with p H response was coated on its surface by in-situ growth method.During this process,metformin（Met）was added to make it inside the nanosystem to prepare nanoparticles Met/MoS₂@ZIF-90.The prepared Met/MoS₂@ZIF-90 was characterized by SEM,UV-vis spectroscopy,FTIR spectroscopy and Zeta potential analysis.The results showed that Met/MoS₂@ZIF-90 nanoparticles with an average particle size of about 150 nm were successfully synthesized.The drug loading of nanoparticles was 20.5%,and the optimal drug release rate was 83.9%.The photothermal conversion efficiency was calculated to be 28.6%.The results of cytotoxicity experiments confirmed the biosafety of Met/MoS₂@ZIF-90 in normal cells.After the nanoparticles were co-cultured with Hep G2 cells,the ATP content in the cells was detected to prove that it had the effect of reducing cell energy metabolism.Under 808 nm light irradiation,heat is generated by photothermal conversion,which causes damage to Hep G2 cells.In the mouse model experiment,Met/MoS₂@ZIF-90 nanoparticles showed high biocompatibility and strong anti-tumor effect.This study demonstrates the effectiveness of photothermal therapy combined with metabolic therapy in anti-tumor therapy,and provides a basis for further research on anti-tumor therapy.（2）With MoS₂ as the basic core,ZIF-90 was grown in situ on its surface.In the process,triptolide（TP）and triphenylphosphine（TPP）were added,and polyethylene glycol（PEG）was coated on the surface of the nanosystem to prepare nanoparticles TPP-TP/MoS₂@ZIF-90@PEG（TTMZP）.The prepared TTMZP was characterized by SEM,UV-vis spectroscopy,FTIR spectroscopy and Zeta potential analysis.The results showed that TTMZP nanoparticles were successfully synthesized with an average particle size of about 182±17.3 nm.The drug loading of nanoparticles was 82.6%,and the optimal release rate was 87.5%.The photothermal conversion efficiency was calculated to be 32.5%.The results of cytotoxicity experiments confirmed the biosafety of TTMZP in normal cells.CCK-8 assay and live and dead staining showed that nanoparticles had a killing effect on Hep G2 cells.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.