肝细胞癌规范化治疗后仍可能存在隐匿及残余病灶，如何早期检出并靶向治疗这些病灶、减少肝细胞癌的复发和转移是提高患者生存率的关键问题。本课题组前期研究表明热化疗可以通过抑制上皮间质转化和Treg细胞介导的免疫逃逸，从而抑制肝细胞癌的生长、复发和转移。在此研究基础上，拟研制一种具有多模态成像及热化疗功能的靶向超声微泡（PFH@PLGA/MNPs/PD-GPC3），通过GPC3抗体靶向肝癌细胞，利用该靶向微泡的磁共振、超声、光声多模态成像功能提高隐匿及残余病灶的检出率，引导肝细胞癌的治疗。该靶向微泡在近红外光激发下, 利用其壳上黑色素纳米粒的热疗作用联合虎杖苷的化疗作用协同抑制肝细胞癌的生长、侵袭和转移，并从上皮间质转化和肿瘤免疫微环境调节两方面揭示其作用机制。本研究为减少肝细胞癌的复发和转移，改善预后，提供新的方法和理论依据。

Occult and residual lesions may still exist after normalized treatment of Hepatocellular carcinoma. Earlier detection together with targeted therapy of the lesions and decrease of recurrence and metastasis are key issues for improvement of the survival rate of patients with hepatocellular carcinoma. Previous studies have demonstrated that thermo-chemotherapy can inhibit the growth, recurrence and metastasis of hepatocellular carcinoma by suppressing epithelial-mesenchymal transition and Treg cell-mediated immune escape. Based on these, brand new targeted ultrasound microbubble (PFH@PLGA/MNPs/PD-GPC3) with the ability of multimodality imaging and thermo-chemotherapy is intended to be developed. GPC3 antibody is able to target hepatocellular carcinoma cells, and multimodality imaging including magnetic resonance imaging, ultrasound imaging, photoacoustic imaging can improve the detection of occult and residual lesions for further guiding the treatment of hepatocellular carcinoma. After stimulating microbubbles with near-infrared light, hyperthermia caused by melanin nanoparticles and the chemotherapeutic effect of polydatin are capable to synergistically inhibit the growth, invasion and metastasis of hepatocellular carcinoma, and the mechanisms involving epithelial-mesenchymal transition and tumor immune microenvironment will be meticulously discussed. This study provides new methods and theoretical basis for improving the prognosis, reducing the recurrence and metastasis of hepatocellular carcinoma.