近红外长余辉纳米材料联合光动力治疗探针诊治肝癌微脉管癌栓的研究

Hepatocellular carcinoma (HCC) is a global problem and the third most common cause of cancer related deaths in the worl. Surgery is the mainstay of Hepatocellular Carcinoma(HCC) treatment. However, tumor recurrence rate complicates 75% of cases at 5 years after resection. Microvascular invasion (MVI) is a powerful validated,independent predictor of early recurrence and poor overall survival (OS) after surgical treatment of HCC。If the surgeon could find and treat MVI in the first time operation, the recurrence rate will be further reduced. We developed a kind of novel nanoparticles (ATFSOC-ZGC-ZnPc), which could target to the u-PA receptors that are highly expressed on the surface of HCC cells. The ATFSOC-ZGC-ZnPc are used for luminescence imaging guidance and used as the built-in excitation source to activate the photosensitizers(ZnPc) for photodynamic therapy (PDT). It will help the surgeons find and treat MVI or primary HCC. Even the MVI or residual cancer in the unresectable region of the liver, the PDT could treat it without damaging more normal liver tissue. Then we could further reduce the recurrence rate of liver cancer after surgery and improve the cure rate of liver cancer.

肝细胞癌(HCC)是世界上第三大最常见的癌症死亡原因。手术仍然是治疗肝癌的首选方法。然而术后5年患者的复发率高达约75%。导致肝癌术后高复发率的最主要因素是肝癌微脉管癌栓的形成。若能在首次手术中发现并治疗微脉管癌栓，将能够降低肝癌术后的复发率，进一步提高肝癌患者的治愈率。本项目将研发一种可靶向肝癌组织u-PAR的纳米探针（ATFSOC-ZGC-ZnPc），利用近红外荧光长余辉纳米材料(ZGC)在体外LED灯冷光源激发后产生近红外荧光特性，实现荧光导航定位肿瘤并内在激发光敏剂(ZnPc)产生光动力治疗作用。从而术中定位肝癌及微脉管癌栓辅助切除病灶，并对不可切除的微脉管癌栓或残余癌灶实现光动力治疗，降低手术后肝癌的复发率，进一步提高肝癌的治愈率。

肝细胞肝癌 (HCC)是世界上第三大最常见的癌症死亡原因，其高患病率和高死亡率的特点已经成为我国居民的重要威胁之一。外科手术仍然是HCC根治的主要治疗手段之一，发现微小病灶，实施精准肝切除，是实现根治性手术切除的关键。术中荧光分子成像(FMI)在辅助外科医生实现精确肿瘤成像方面显示出巨大潜力。近年来靶向联合免疫治疗为晚期肝细胞癌特别是伴有癌栓的HCC的转化治疗提供了有效的治疗方案，靶免治疗的肿瘤分子显像将有助于治疗效果的评估。本项目聚焦肝癌演进中的核心分子CD24及肿瘤相关巨噬细胞上与之匹配的免疫检查点Siglec-10，探究其相互作用触发“不要吃我”信号传导引起肿瘤免疫逃逸的分子显像，研发近红外区（NIR）探针并实现了在动物层面的初步应用。同时，本项目也应用影像组学技术，以脑胶质瘤为模型，开发了基于荧光成像的深度卷积神经网络系统，实时动态可视化的提升了检测灵敏度，协助外科医生实施术中肿瘤边界的确定，优化术中决策，提高判断准确性并预测肿瘤病理分期及Ki67表达水平。将该算法迁移后，应用范围将能够扩展至更为复杂的肝癌模型，为实现肝癌精准切除提供术中导航的实时成像系统。