The Study On Early Diagnosis And Treatment Of Small Hepatocellular Carcinoma By GPC-3-targeted Nanoparticles

BackgroundDespite advancements in diagnostic methods and therapeutic strategies,the mortality rate of hepatocellular carcinoma(HCC)remains as high as its incidence rate.Most liver cancers are detected in the advanced stages,when treatment options are limited.Small HCC is difficult to diagnose and is often overlooked by current imaging methods because of the complexity of the liver environment,especially in cirrhotic livers.In the present study,we developed a tumor "cruise missile." Using this tool,small HCCs in the complex liver environment can be located by targeted-multimodal technology and then destroyed by sequential catalytic nanomedicines.ObjectiveThe purpose of this study was to capture the key points of early small HCC formation and typical characteristics in imaging in complex liver environments,and then facilitated targeted therapy.It will make a meaningful contribution to the early diagnosis and treatment of HCC and lay a foundation for the functional visualization of HCC in vivo in the future.MethodFirstly,the specific expression of GPC3 in HCC was verified at the level of cells,animals,and human tissues.Secondly,FGP nanoparticles were synthesized and characterization were tested.Furthermore,validation of the specificity of FGP NPs for liver cancer were confirmed in HCC cells,mouse HCC models and human HCC tissues.Subsequently,at different week of carcinogen-induced HCC models,the changes in liver structure were monitored dynamically by using a PAI/US technique to obtain the key time points of HCC formation and its unique imaging characteristics.Finally,effective sequential catalytic therapy was performed on HCC mice.ResultsIt was proved by experiments that GPC3 targeting peptides were indeed attached to the surface of FGP NPs,and the mesopores contained glucose oxidase(GOD).And it has good photoacoustic signal and could targeted to HCC.In a carcinogen-induced mouse HCC model,FGP NPs could be used to accurately diagnose HCC in a liver cirrhosis background as well as distinguish HCC nodules from other abnormal liver nodules,such as cirrhosis nodules and necrotic nodules,by dynamic contrast-enhanced PAI.Then,highly reactive oxygen species were formed by sequential catalytic reactions,increasing the survival of the model mice.The novel strategy was designed to enhance the accuracy of small HCC visualization to 85.7%using PAI in complex liver environment,which then facilitated sequential catalytic targeted therapy for small HCC.ConclusionIn summary,our results indicated that combined US/PAI could detect small HCCs in complex liver environments as well as be used as an imaging guide for targeting sequential catalytic treatment for small HCCs.The present study provides a basis for the precise detection and elimination of small HCCs in the complex liver environment.