The Synthesis Of Novel Fluorescent Nanocomposites And Their Application For Hepatocellular Carcinoma Intraoperative Navigation And Sonodynamic Therapy

Cancer is threatening to human health seriously and causing enormous social burden.Liver cancer is the most common malignant tumor in the clinic with high morbidity and mortality.The precision medicine is a kind of individualized treatment which was developed by the development of nanomedicine and making tumor cure possible.In view of the advantages of nanotechnology and its application in cancer diagnosis and treatment,we have designed nanomaterials that can be used for imaging and treatment,and explored the application of different nanomaterials in intraoperative navigation and sonodynamic therapy(SDT)of liver cancer.In chapter 1,we introduced advantages and disadvantages of the liver cancer treatment methods,and mainly focus on the encountered problems during the operation and the various limitations of traditional treatment methods.We also introduce the development of molecular imaging and the opportunities for cancer diagnosis and treatment due to the innovation in new methods.We disscuss the promoting in molecular imaging and precise treatment of cancer by development of nanotechnology.The combination of nanotechnology with fluorescence intraoperative navigation can achieve precise resection of liver cancer,and the combination of nanotechnology with emerging therapeutic strategies can achieve high specificity and high efficiency of SDT for liver cancer.In chapter 2,we synthesized a safe and stable ICG-lipidol nanoemulsion with the clinically-approved ICG,iodized oil,Tween-80 and lecithin using emulsification technology.It can realize CT and photoacoustic imaging for diagnosis of orthotopic liver cancer,and achieve the fluorescence imaging guides surgical resection during surgery,reducing surgical residual and reducing postoperative recurrence.Our results suggest that the synthesized ICG-lipidol nanoemulsion can enhance the fluorescence intensity and stability of the ICG,improve the signal-to-noise ratio(tumor/liver)of fluorescence imaging.The results also confirmed that ICG-lipidol nanoemulsion has a good orthotopic liver cancer fluorescence intraoperative navigation effect.In chapter 3,basing on the advantages and problems of SDT and the advantages of metal-organic nanoparticles,we synthesized nanosonosensitizers with iron ions and sonosensitizers,and modifeid with liver cancer tissue targeted peptide to enhance drug accumulation in the tumor.Meanwhile,the nano-sonosensitizers can enhance the SDT effect by down-regulating the expression of intracellular antioxidant enzyme SOD2 through loading specific siRNA.The Fe3+of nanosonosensitizers can not only decrease the intracellular antioxidant GSH,but also further generate cascade Fenton reaction to produce hydroxyl radicals,which can improve the SDT effect.The nanosonosensitizers can accumulate in tumor through the EPR effect and the targeted effect of RGD,and enhance SDT effect through multiple channels and mechanisms.In particular,nanosonosensitizers tracing and therapeutic effect monitoring are also achieved by fluorescence(FL)/magnetic resonance(MR)imaging.