| Mesoporous silica nanoparticle is a kind of inorganic nanoparticles which is easily ingested by cells with good biocompatibility.Its structure is stable and easy to be modified,and its application in drug delivery is increasing.A targeted drug-loaded mesoporous silica system was developed in this study.The EGFR antibody was attached to the surface of the mesoporous silica and contained gemcitabine to explore its role in the treatment of pancreatic cancer by combining with HIFU.This study mainly carry out the following work.Mesoporous silica nanoparticles were preparared and its safety detected.Experiments show that MSNs are toxic to HUVECs at high concentrations.MSNs mainly cause cell necrosis rather than apoptosis.High concentrations of MSNs block cell cycle,so that a large number of cells blocked in G1 phase.High doses of MSNs have an impact on the mouse liver biochemical indicators,which will aslo cause damage to liver and lungs for long time sustained effect.Targetd gemcitabine-loaded MSNs system was prepared and the successful connection of antibodies and drug loading were verified.In addition,the fixed suture method of nude mice dorsal skin window chamber was innovatively changed to pins and fixed cap,which were easy to operate.Window material was changed from metal to plexiglass,so that the load of nude mice was reduced.The uniform distribution of the targeted drug-loaded MSNs in the mouse was observed in the window chamber,indicating that the targeted drug-loaded MSNs were diffused through the blood vessels and entered the body.The vitro cell experiments showed that targeting drug-loaded MSNs increased aggregation of nanoparticles around tumor cells,demonstrating good targeting properties.The vivo tests showed they had better anti-tumor effect.In targeting drug-loaded MSNs combined with HIFU treatment,the MSNs group have obvious advantages in irradiation area coagulation necrosis volume and pathology compared with other groups,confirmed that MSNs enhanced HIFU ablation. |
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