| BackgroundAccording to the statistics of the International Agency for Research on Cancer(IARC)of the World Health Organization(WHO),in 2020,the number of new cases of liver cancer in the world is 910,000,and the number of deaths due to liver cancer is 630,000.At present,liver cancer is the sixth incidence and third cause of death of malignant tumor in the world.Moreover,the overall 5-year survival rate of HCC patients is less than 18%.The main reason is that clinical imaging examination methods mainly focus on morphological diagnosis and lack of technical means for accurate diagnosis and treatment of early HCC at the molecular and cellular levels.With the development of molecular imaging diagnostic technology,photoacoustic imaging emerges at the historic moment.Because it covers the advantages of high penetration depth of acoustic imaging and high resolution of optical imaging,especially the greater penetration depth of NIR-? photoacoustic imaging,it has a great application prospect in deep location and rich blood supply of liver cancer tissue imaging.In recent years,the research on photoacoustic imaging of liver cancer mainly focuses on the research after the formation of liver cancer,but there are few studies on local angiogenesis,blood flow,blood oxygen and other changes during the evolution of early liver cancer.Based on the above clinical problems,this study intends to conduct photoacoustic multimode imaging and in vivo visualization of key molecular functions on the key nodes in the evolution of liver cancer,so as to realize early diagnosis and early treatment of liver cancer in a true sense.ObjectiveIt is planned to explore the changes at the molecular and cellular levels during the evolution of liver cancer through photoacoustic multimode imaging equipment.Subsequently,a novel NIR-? hepatocellular carcinoma specific photoacoustic nanoprobe was prepared and the in vivo visualized diagnosis and treatment of key molecular functions of early hepatocellular carcinoma was studied.MethodsIn this study,we will use photoacoustic multimode imaging equipment photoacoustic tomography(PACT)and acoustic resolution photoacoustic microscopy(AR-PAM)to monitor the changes of local blood vessels,blood flow and blood oxygen during the HepG2 cell implantation to early HCC formation in nude mice,so as to explore the time point of early HCC formation.Based on the liver cancer model studied above,a specific targeting nano-probe for liver cancer with NIR-?photoacoustic and photothermal properties Pt@PDA-c was synthesized by coating platinum particles with polydopamine,modifying PEG and attaching CXCR4 target.After verifying its in vitro characterization and cell-level properties,in vivo visualization of the function of key molecules and non-invasive NIR-? photothermal therapy were performed in a nude mouse hepatocellular carcinoma model.ResultsIn this study,photoacoustic multimode imaging equipment(AR-PAM and PACT)was used to preclude that the average time of increased angiogenesis,hemoglobin concentration and oxygen saturation from HepG2 cell implantation to early HCC formation in nude mice was 120?168 hours.The hepatocellular carcinoma specific targeting nanoprobe Pt@PDA-c was successfully prepared,and its suitable particle size(150 nm),good photoacoustic imaging,photothermal therapy performance,good biocompatibility and stability were verified.After verification of its efficacy at the cellular level,in vivo visualization of the function of the key molecule CXCR4,non-invasive NIR-? photothermal ablation and efficacy evaluation were successfully performed in subcutaneous and in situ small hepatocellular carcinoma models in nude mice.ConclusionIn this study,the time from subcutaneous HCC cell implantation to early HCC formation in nude mice was 120?168 hours.The precise photoacoustic diagnosis and photothermal treatment of non-invasive liver cancer were carried out based on the specific targeting nanoprobe for liver cancer Pt@PDA-c,which provided a new idea for the application and promotion of nanomedicine in photoacoustic diagnosis and treatment. |
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