| BackgroundPrimary liver cancer is one of the most common malignant tumors in the world.China is a big country with liver cancer,and more than half of the new and dead liver cancer cases come from China every year.The new cases and deaths of liver cancer are also increasing year by year in the world,which seriously threatens the health and economic level of people around the world.Due to the insidious onset of liver cancer in the early stage,the resolution of traditional imaging diagnosis is low,especially for tumors with a diameter<1 cm,it is difficult to achieve accurate diagnosis.In addition,the overall 5-year survival rate of liver cancer patients is less than 18%,and the 5-year survival rate of small liver cancer patients with early diagnosis and treatment can be increased to 60%-80%,which is the main method to improve the prognosis of patients.At present,there is a lack of early diagnosis and treatment methods for liver cancer in clinical practice,and more effective liver cancer diagnosis methods and anti-tumor solutions are still needed.In recent years,photoacoustic imaging(PAI),as a new type of non-invasive imaging method,has a remarkable performance in tumor imaging.Due to its high tissue resolution and sensitivity,it has the advantages of both optics and acoustics,and can image tumors from multiple levels.At the same time,the combination of magnetic resonance imaging(MRI)can improve the sensitivity and resolution of imaging.Good results in diagnosis and treatment.In this study,a photoacoustic/magnetic resonance multi-mode imaging nanoprobe was designed,which not only possesses photoacoustic and magnetic resonance signals,but also specifically recognizes the key molecule EpCAM on hepatoma cells.In addition,the photothermal effect of the nanoprobe can be used to precisely and effectively kill tumor cells to achieve a therapeutic effect.Therefore,this study intends to study the key time nodes of liver cancer evolution,the diagnosis and treatment of early liver cancer,and the in vivo visualization of key molecules through specific targeted probes.ObjectiveIn this study,photoacoustic imaging was used to study the key time nodes in the evolution of liver cancer.At the same time,EpCAM-targeted liposome-encapsulated melanin nanoprobes(Mel@Lip-EpCAM)were prepared,and combined with PAI/MRI for in vivo detection of early-stage liver cancer.for visual diagnosis and treatment.Method1.Multispectral Optoacoustic Tomography(MSOT)will be used in this study to monitor the changes of blood vessels and blood oxygen saturation in the tumor cell seeded area during the process of subcutaneously implanting hepatoma cells HepG2 to forming early liver cancer in nude mice.To explore the key time nodes in the evolution of liver cancer.2.To establish a liver cancer in situ tumor model in nude mice,and to synthesize a targeted probe Mel@Lip-EpCAM with photoacoustic,magnetic resonance imaging and photothermal effects through liposome-encapsulated melanin nanoparticles and external anti-EpCAM antibody,to detect its characterization,cytotoxicity,targeting,and photothermal efficacy,and use the nude mouse liver cancer in situ tumor model for in vivo visualization and photothermal therapy(PTT).3.To verify the clinical human liver cancer tissue,hepatocellular carcinoma(HCC)tissue,HCC adjacent tissue,and normal liver tissue were incubated with the probe,respectively,and three different tissues before and after incubation were used for imaging.Result1.In this study,the multispectral photoacoustic imaging system(MSOT)was used to scan and image subcutaneous tumors in nude mice.The preliminary results showed that the increase of blood vessels and blood oxygen saturation in the process of HepG2 hepatoma cells from injection and implantation to the formation of pathologically verified hepatocellular carcinoma tumors The time required for the rise is 96 to 120 hours;2.The liver cancer-specific targeting probe Mel@Lip-EpCAM was successfully synthesized.It was verified by experiments that it has suitable particle size,stable properties,good biocompatibility,and has good photoacoustic imaging and magnetic resonance imaging effects.Photothermal efficiency.PTT was performed on the nude mouse orthotopic tumor model,and the tumor treatment effect was good,and the survival rate of nude mice was high;3.After MSOT scans human liver cancer tissue,adjacent tissue,and normal liver tissue,the preliminary results show that the photoacoustic signal of human liver cancer tissue after incubation of the probe has a significant increase,indicating that it binds more to Mel@Lip-EpCAM.The photoacoustic signals of the para-cancerous and normal liver tissues did not increase significantly,indicating that Mel@Lip-EpCAM was basically not combined.ConclusionThis study preliminarily explores the key time point from the injection of subcutaneous tumors in nude mice to the formation of early-stage hepatocellular carcinoma;design and synthesis of a novel dual-modality active targeting nanoprobe Mel@Lip-EpCAM,which can realize optical The advantages of acoustic-magnetic resonance imaging are complementary to diagnose early-stage liver cancer,and precise targeted photothermal therapy can be used for non-invasive treatment of early-stage liver cancer.In addition,under photoacoustic imaging,Mel@Lip-EpCAM can clearly distinguish human liver cancer tissue from normal liver tissue,which provides a preliminary experimental basis for the in vivo visualization of early-stage liver cancer. |
PDF Full Text Request