In Vivo And Vitro Investigation Of Nano-mesoporous Titanium Dioxide Drug Delivery System With A "Switch "

With the rapid development of nano drug delivery system,in recent years,various strategies which were used to kill cancer cells effectively in the drug delivery system have been gradually developed.Among them,the stimuli-responsive controllable release drug delivery system is very popular due to its significant advantages.In this study,we have investigate an nano-mesoporous TiO₂ drug delivery system that the release can be controlled through ultrasound.This paper had made a preliminary study in vitro anti-tumor experiments and in vivo anti-tumor experiments.mTiO₂ mesoporousnanoparticles were synthesized by Sol-gel method and its diameter is about 170 nm,then it was loaded with the chemotherapy drug docetaxel（Docetaxel,DTX）,and was wrapped with double-stranded PEI.The preparation has the characteristics of good biocompatibility,low toxicity and stable structure.In the blood circulation process,because the nanoparticles was wrapped with PEI,anti-tumor drug DTX can not be released;but when it has reached the tumor site,we used near IR laser irradiation treatment,and PEI was breaked,so the drugs were releasedfrom the coreand killed cancer cells.In conclusion,the preparation has two advantages:First,under the treatment ofIR irradiation,mTiO₂ can produce reactive oxygen species（Reactive oxygen,ROS）,and PEIwere cut,so the antitumor drug DTX were released rapidly.In this way,we have achievedreleasing the drugcontrollable in the tumor site.What is more,we have achieved improving the drug’s efficacy and avoided the systemic side effects;Second,ROS can also damage the mitochondria and DNA in tumor cells,so achieved the synergistic effect of photodynamics therapy and chemotherapy.In vitro antitumor experiments,we researched the antitumor efficacy of mTiO₂@DTX-PEI preparation on MCF-7 cell,and we also examined the intake situation.As a result,the cell inhibition rate of the preparation without IR irradiation treatment only is about 5 %;when the IR irradiation time increased to 20 s,the inhibition rate increased to 40%.The result indicated that the preparation’s chemotherapy and acousticdynamics therapy effectwas obvious under laser irradiation.In vivo antitumor experiments:we examined the anti-tumor effect.of the preparation in tumor-bearing mice.Results showed that,pure titanium oxide carrier owned good biocompatibility and low toxicity side effects,but it can not kill cancer cells;Compared with the DTX,mTiO₂ @ DTX-PEI can control the release of DTX only in tumor bylaser irradiation thus avoided the DTX bone marrow suppression side effects and liver,spleen toxic side effects,and reduced systemic toxicity of DTX in a large extent.The preparation can be effectively enriched in the tumor site,and showed significant antitumor efficacy.After 5 times treatment with tail vein injection,tumor volume decreased by about 40%.