Preparation Of Drug Delivery System Based On Different Carriers For Antitumor Research By Using Prodrug Technology

Objective: To explore the preparation and anti-tumor application of nano-drug delivery systems(DOX @ MSN-PTX @ PSS and DOX @ ZIF-8-FA)based on prodrug technology.Methods : By chemical synthesis,paclitaxel(PTX)and doxorubicin(DOX)were prepared into prodrugs PTX-SS-COOH and CAD,respectively.Two prodrugs were combined with mesoporous silicon MSN and zeolite imidazole framework ZIF-8 to prepare two nano-delivery systems DOX@MSN-PTX@PSS and DOX@ZIF-8-FA.Particle size,zeta potential,drug loading and drug release of nano-formulations under different p H,redox and other conditions were investigated.In the DOX@MSNPTX@PSS nano drug delivery system,the toxic effect of the nano preparation on BT-549 breast cancer cells and MCF-10 A healthy cells were detected by WST-1 cytotoxicity experiment,confocal positioning experiment,flow cytometry and other experiments.At the same time,in the DOX@ZIF-8-FA nano preparation system,through the WST-1 cytotoxicity experiment,confocal localization experiment,flow cytometry experiment,tumor volume observation,mice weight change,Bio-Real in vivo imaging experiments,the inhibitory effect of DOX@ZIF-8-FA nano-formulation on MDA-MB-231 cancer cells in vitro and its distribution in vivo,as well as the inhibitory effect on transplanted MDA-MB-231 breast cancer in vivo were examined.Conclusion: In this paper,the DOX@MSN-PTX@PSS nano-delivery system significantly improves the drug loading efficiency of PTX.By adjusting the optimal drug loading ratio of PTX/DOX,the best synergistic effect can be achieved.PTX-SSCOOH can achieve redox sensitive tumor specific drug releasing and PSS can realize the p H-sensitive release of drugs through electrostatic attraction,and increase the cavernous endocytosis of cancer cells BT-549,improve the efficacy of nanoparticles,and also neutralize the surface potential of nanoparticles,reducing the specific phagocytosis of healthy cells.And through in vitro release and cell experiments proved that the nanoparticles can not only be specifically released under reducing conditions and acidic conditions at the tumor site,but also achieve the combined treatment of DOX and PTX.At the same time,in the DOX@ZIF-8-FA nano-delivery system,by modifying the drug,the affinity between the drug and the carrier is greatly improved,the drug load is increased and the burst effect is reduced.The problem that the surface of the zif-8 system cannot be modified was solved.Then through the cytotoxicity test,confocal imaging,flow cytometry and small animal imaging and other experiments proved the safety and targeting of nanoparticles.In short,this article prepared two kinds of prodrugs combined with different nanocarriers,which broadened the application range of prodrugs from multiple angles.