抗glypican-3纳米抗体/抗菌肽融合蛋白对肝癌小鼠的靶向治疗

早期诊断和治疗是提高原发性肝细胞癌疗效的关键因素之一。磷脂酰肌醇蛋白聚糖3（Glypican 3, GPC3）与原发性肝癌的发生、发展密切相关，在肝癌早期呈高表达，对早期原发性肝细胞癌具有诊断价值。本研究拟采用GPC3为靶点，构建新疆双峰驼纳米抗体噬菌体展示文库，并从中筛选获得具有较高抗原结合活性的抗GPC3的纳米抗体，将其与新疆家蚕抗菌肽进行耦联，由其介导抗菌肽与肿瘤细胞结合，达到特异性杀伤肝癌肿瘤的效应。研究主要包括：1. 具有较高结合活性的抗GPC3骆驼纳米抗体的筛选；2. 具有肿瘤靶向性抗菌肽的制备及性质研究；3. 具有肿瘤靶向性抗菌肽体内外抗肿瘤作用研究。本研究以抗菌肽特殊的抗肿瘤作用机理为基础，结合纳米抗体不同的靶向性，为抗菌肽更有效的应用于临床抗肿瘤药物的开发及肝癌的分子靶向治疗提供解决方案。

Early diagnosis and treatment is one of the key factors to improve the prognosis of hepatocellular carcinoma (HCC). Glypican-3 (GPC3) contributes to the initiation and progression of HCC. high expression of GPC3 has the diagnostic value for HCC. This research intends to target GPC3 by construction of the nanobody phage display libraries from Xinjiang Bactrian camel, and affinity screening of anti-GPC3 nanobodies with higher antigen binding afinity. The anti-GPC3 nanobodies will be coupled with the antibacterial peptides to achieve the effect of specific killing of liver cancer cells. The research mainly includes: 1. The camel nanobody as screening platform targets molecular markers in tumor; 2. Preparation of the HCC-targeting antibacterial peptide; 3. The anti-tumor effect of HCC-targeting antibacterial peptide in vitro and in vivo. In this study, the special antitumor mechanism of antibacterial peptide will be combined with different target-based nanobody. The study will provide solutions for the application of antimicrobial peptides as potential antitumor drugs and targeted therapy of HCC.