The Synthesis And Reserch Of Biological Activity In Vitro Of Mesoporous Silica Nanocomposites

Chemotherapy is the main method of cancer treatment,but many chemotherapeutic drugs are prone to drug resistance and have toxic side effects that limit their use.Because of its unique properties,nanomaterials have shown great advantages in the treatment and diagnosis of cancer.The emergence of nanomedicines has provided new opportunities for cancer treatment.The use of drug delivery systems to deliver drugs can overcome drug resistance,reduce toxic side effects,and improve the therapeutic effects of drugs.Mesoporous Silica Nanoparticles(MSNs)have attracted attention because of their unique structural features such as high specific surface area,large pore volume,variable particle size pore size,and high thermal stability.The carrier has great advantages such as low toxicity,good biocompatibility,and high drug loading.At the same time,its surface modification can achieve targeted and controlled release of drugs,to improve the efficacy of drugs,reduce the toxic and side effects,which is of great significance for cancer treatment.Hyaluronic acid(HA)is an important component of the extracellular matrix,has good biocompatibility,can specifically bind to the CD44 receptor,and the presence of hyaluronidase in the tumor microenvironment can degrade HA.Therefore,MSN encapsulated with HA can slow down the early release of drugs,increase the selectivity of nanomedicines,and reduce toxic and side effects.Folic acid(FA)is a water-soluble B vitamin that specifically binds to folate receptors and is highly expressed on the surface of many tumor cells.Therefore,the use of FA modified MSN carrier drugs can enhance the targeting of nanomedicine.This paper mainly combines the advantages of MSN in drug delivery.It uses HA and FA to modify MSN and study the application of modified MSN in drug delivery.The research content of this article mainly includes the following two aspects:1.We first synthesized two organic conjugates of nitrogen mustard-coumarin(DJ-XDS)and 5-fluorouracil-coumarin(5-FUA-4C-XDS).MSN was then prepared by a sol-gel method,and MSN was modified with a disulfide bond to give MSN-SS-CS.The two organic conjugates were loaded on MSN-SS-CS and coated with HA,respectively.MSN-SS-CS@DJ-XDS/HA and MSN-SS-CS@5-FUA-4C-XDS/HA are two MSN nanocomplexes.Characterization of MSN and MSN nanocomposites by transmission electron microscopy(TEM),Zeta potential analyzer,UV-vis spectrophotometer(UV-vis),FT-IR spectrometer(FT-IR)and thermogravimetric analyzer(TGA).MTT assay was used to detect the in vitro biological activity of MSN and MSN nanocomplexes.MSN and MSN nanocomplexes were treated with HCT-116,HeLa,and QSG-7701 cells.The experimental results showed that MSN material was almost non-toxic to cells.The toxicity of MSN nanocomposites after loading organic conjugates was significantly enhanced.Next,we used flow cytometry and high content imaging to analyze the apoptosis of the nanocomplex and HCT-116 cells,and to detect mitochondrial membrane potential(MMP)and intracellular reactive oxygen species(ROS)changes.We found that MSN nanocomplexes can reduce MMPs,increase ROS,and induce apoptosis.2.We first modified the surface of MSN with FA to obtain MSN-FA,labeled MSNs and MSN-FA with FITC(marked as FMSN and FMSN-FA,respectively),and used TEM,Zeta potential,UV-vis,FT-IR and TGA were used to characterize the MSN before and after modification.It was found that FA was well modified on the surface of MSN,and FITC successfully labeled the nanomaterial.Next,10-hydroxycamptothecin(HCPT)was loaded with MSN and MSN-FA to obtain two kinds of MSN@HCPT and MSN-FA@HCPT nano drug delivery systems.Cellular absorption experiments demonstrated that FA modified MSN is more likely to enter HeLa cells(high expression of folate receptor).The MTT cytotoxicity experiment showed that the drug-loading system after adsorbing HCPT had a good anti-tumor activity,and the activity of the FA-modified drug-loading system was stronger,which proved that FA has a certain targeting ability.In addition,we performed apoptosis-related experiments to detect changes in MMP and ROS content.The experimental results show that both MSN@HCPT and MSN-FA@HCPT drug delivery systems can induce apoptosis,decrease MMP content and increase ROS content,and the effect of FA-modified drug delivery system is more obvious,again proving FA.Modified drug delivery system can enhance the targeting and improve the therapeutic effect.