Studies On Microbeads Containing Silica-doxorubicin Nanomedicine For Chemoembolizaiton Of Hepatocellular Carcinoma

With the continuous development of society,more and more people's lifestyles have changed,and this change is accompanied by more and more health problems,cancer is the "questionable answer" that all people in these issues cannot avoid.Currently,there are more than 100 types of cancer known to affect human beings,which may cause symptoms such as lump,abnormal bleeding,prolonged cough,fever,excessive fatigue,unexplained weight loss,and changes in defecation.The treatment of cancer continues from the date the cancer was discovered.In addition to traditional surgery,radiotherapy and chemotherapy,many new research results have been used for the clinical treatment of cancers.This dissertation focused on the silica nanoparticle drug deliver system which was combined with gelatin embolism microspheres for the targeted interventional chemoembolization of solid tumors represented by liver cancer.The specific research results showed as follows:1.Using a modified Stober method,silica nanoparticles(SNPs,SNPs-NH2,SNP-SH)with specific functional groups are synthesized directly in the aqueous phase and SNP-SO3H was prepared by oxidation of SNP-SH.Through various characterizations and tests,it was proved that the modified SNPs were successfully modified.The results of SEM and TEM presented the size,size distribution and morphology of the modified SNPs.The modified SNPs were potentially served as a nano drug delivery system,and its own toxicity-against cells and organisms must be considered carefully.In this research,mouse fibroblasts(L929)and gastric cancer cells(SGC7901)were subjected to a preliminary in vitro cytotoxicity array on SNP,SNP-NH2 and SNP-SO3H.The results showed that the modified nano-silica particles did not exhibit obvious cytotoxicity,Silicon particles satisfied the basic requirements for serving as a nanocarrier drug delivery system.2.Selecting Doxorubicin(DOX)as model drug,we prepared DOX@SNP-NH2 and DOX@SNP-SO3H nano medicine according to the impregnation method.Then,it was investigated the drug released properties of DOX@SNP-NH2 and DOX@SNP-SO3H.The results showed that DOX@SNP-SO3H has better performance than DOX@NH2,DOX@SNP-SO3H exhibited 55%drug loading content and 70%drug releasing in 48 hours.The effects of charge distribution of SNP-SO3H on the drug loading process have also been investigated by adjusting the pH value of environment.It was found that the optimal conditions for loading DOX is when pH equals to 11 and the DOX loading cotent is about 140%.Based on a series of cytotoxicity tests,it could be concluded that SNP-SO3H is potentially be applied as a drug delivery vehicle.3.Gelatin Micro Beads(GMB)for embolization were prepared to use a T-type microfluidic chip,and a number of factors including gelatin solution viscosity,concentration of surfactant Span 80,the flow rate of aqueous phase and organic phase,temperature and genipin concentration were examined.Under the best conditions,100?m GMBs were prepared sucessfully,and then DOX@SNP-SO3H/GMB were also prepared to use the same method.Hemolysis test and plasma recalcification test showed that both GMB and DOX@SNP-SO3H/GMB presented perfect blood compatibility.Both GMB and DOX@SNP-SO3H/GMB demonstrated excellent cell-compatibility in cytotoxicity array.The preliminary animal test on VX2 rabbit showed the successful embolization in the vessles of cancer tissue with interventional treatment.