Functional Modification Of Silicon-based Janus Nanomaterials And Research On Drug Loading And In Vitro Release

An anti-tumor drug delivery system is a drug delivery system that uses non-toxic/less toxic particles as an anti-tumor drug carrier,and is modified by surface functionalization to act on tumor cells to form a drug delivery system.Common anti-tumor drug carriers include:mesoporous silica,hydrogels,liposomes,polymer micelles and so on.Modifications with different functional groups(folate,hyaluronic acid,etc.)can increase the targeting of tumor cells,reduce damage to normal cells,and greatly reduce the toxic and side effects of chemotherapy drugs on the body;various Modification of stimulus-responsive groups(redox stimulus responsive,p H stimulus responsive,etc.)enables the drug delivery system to achieve sustained and controlled drug release;functionally modified drug carriers can enhance the high permeability and retention of the carrier system(EPR)effect to increase the degree of accumulation of nanocarriers in tumor sites.These advantages have led to rapid development of anti-tumor drug delivery systems.Silicon-based Janus nanoparticles(JNPs)are one of the most promising nanocarriers in mesoporous nanocarriers.Compared with homogeneous nanoparticles,JNPs with dual-compartment or dual-surface functional modification can achieve dual functions or multifunctional delivery.Nanomaterials of different properties can be specifically combined together,overcoming the limitations of a single material used in drug delivery systems,achieving a variety of treatment methods,and enabling more precise and controllable delivery of drugs to targeted sites,thereby Effectively reduce the toxic and side effects on normal tissues.In this thesis,on the surface of different spherical metal oxides(TiO₂and Fe₃O₄)nanoparticles,the rod-like structure of mesoporous silica was grown by the seed anisotropy growth method to obtain two kinds of ball-rod structure silicon-based Janus nanoparticles(T-MSNs JNPs,M-MSNs JNPs);By grafting disulfide bonds,two-terminal amino polyethylene glycol(NH₂-PEG-NH₂)and folic acid(FA),a drug delivery system with folic acid targeting and redox responsiveness(DOX@JNPs-S-S-PEG-FA).And to study its biocompatibility,the model drug doxorubicin(DOX)carrying and in vitro release performance and cell uptake characteristics.The specific research work is as follows:(1)In this paper,using different metal balls as the core,two kinds of sphere-rod structure silicon-based Janus nanoparticles(T-MSNs JNPs and M-MSNs JNPs)were prepared by seed anisotropy growth method.Among them,the S_BETof M-MSN JNPs is 424.133 m²g^-1,the pore volume is 0.313 cm³g^-1,and the average pore diameter is3.908 nm;the S_BETof T-MSN JNPs is 723.496 m2g^-1,the pore volume is 0.655 cm3g^-1,and the average pore diameter is 3.379 nm.By constructing disulfide bonds on its surface and performing carboxylation modification,its carrying rate for the model anti-tumor drug doxorubicin(DOX)is 11.502%(M-MSNs JNPs)and 12.623%(T-MSNs JNPs),respectively.At the same time,through the drug release kinetics fitting,the drug release mechanism is explored,and it is found that the drug release mode is the disconnection of covalent bonds.(2)After the carboxylation modification,the two-terminal amino polyethylene glycol is used as the"intermediate"to connect T/M-MSNs JNPs-COOH and the targeting group folic acid(FA)together.Amino-terminated polyethylene glycol acts as a blocking agent to construct a silicon-based Janus drug delivery system.Through infrared spectroscopy and hydrogen nuclear magnetic spectroscopy,it is proved that polyethylene glycol modified with double-terminal amino group was successfully prepared.Through FTIR,X-ray diffraction,Zeta potential,and thermogravimetric analysis methods,it is proved that the terminal polyethylene glycol as an intermediate group successfully combines the carboxylated silicon-based JNPs with folic acid.(3)Through hemolysis experiments,it is found that JNPs modified with end group polyethylene glycol have good blood compatibility.The hemolysis rates of T-MSNs JNPs-S-S-PEG and M-MSNs JNPs-S-S-PEG with a sample concentration of800?g/mL were only 2.97%and 1.59%.At the same concentration,the hemolysis rates of T-MSNs JNPs and M-MSNs JNPs were 19.88%and 3.23%,respectively.The MTT method was used to evaluate the cytotoxicity of different types of drug delivery systems to Hela cells,and it was found that the viability values of T/M-MSNs JNPs and T/M-MSNs JNPs-S-S-PEG-FA for Hela cells both exceeded 95%.It shows that T/M-MSNs JNPs and T/M-MSNs JNPs-S-S-PEG-FA have good biocompatibility.At a concentration of 100?g/mL,the difference in cell viability of the two drug delivery systems(DOX@T/M-MSNs JNPs-SS-PEG-FA)compared with free DOX is less than5%for Hela cells,indicating the two drug delivery systems have good biocompatibility.(4)Through cell uptake experiments,it is found that the red fluorescence(DOX)intensity of DOX@T/M-MSNs JNPs-S-S-PEG-FA is more significant than DOX@T/M-MSNs JNPs.In the apoptosis experiment,it was found that for the folic acid modified drug delivery system,the two drug delivery systems had the highest cell apoptosis rate,indicating that the constructed folic acid targeted drug delivery system enhanced the targeting ability to Hela cells.