Delivery of tumor-specific inhibitors is a challenge in cancer treatment. Antibody-modified nanoparticles can deliver their loaded drugs to tumor cells that overexpress specific tumor-associated antigens. Here, we constructed sorafenib-loaded polyethylene glycol-b-PLGA polymer nanoparticles modified with antibody hGC33 to glypican-3 (GPC3 +), a membrane protein overexpressed in hepatocellular carcinoma. We found that hGC33-modified NPs (hGC33-SFB-NP) targeted GPC3⁺ hepatocellular carcinoma (HCC) cells by specifically binding to GPC3 on the surface of HCC cells, inhibited Wnt-induced signal transduction, and inhibited HCC cells in G0/1 by down-regulating cyclin D1 expression, thus attenuating HCC cell migration by inhibiting epithelial–mesenchymal transition. hGC33-SFB-NP inhibited the migration, cycle progression, and proliferation of HCC cells by inhibiting the Ras/Raf/MAPK pathway and the Wnt pathway in tandem with GPC3 molecules, respectively. hGC33-SFB-NP inhibited the growth of liver cancer in vivo and improved the survival rate of tumor-bearing mice. We conclude that hGC33 increases the targeting of SFB-NP to HCC cells. hGC33-SFB-NP synergistically inhibits the progression of HCC by blocking the Wnt pathway and the Ras/Raf/MAPK pathway.

肿瘤特异性抑制剂的递送是癌症治疗中的挑战。抗体修饰的纳米颗粒可以将其负载的药物递送至过表达特定肿瘤相关抗原的肿瘤细胞。在这里，我们构建了索拉非尼负载的聚乙二醇-b-PLGA聚合物纳米颗粒，该纳米颗粒用针对肝细胞癌过表达的膜蛋白glypican-3（GPC3 +）的hGC33抗体修饰。我们发现，hGC33修饰的NP（hGC33-SFB-NP）靶向GPC3 ⁺肝细胞癌（HCC）细胞通过与HCC细胞表面的GPC3特异性结合，抑制Wnt诱导的信号转导，并通过下调cyclin D1的表达来抑制G0 / 1中的HCC细胞，从而通过抑制上皮细胞而减弱HCC细胞迁移。间质过渡。hGC33-SFB-NP分别与GPC3分子同时抑制Ras / Raf / MAPK途径和Wnt途径，从而抑制了HCC细胞的迁移，周期进程和增殖。hGC33-SFB-NP在体内抑制肝癌的生长，并提高荷瘤小鼠的存活率。我们得出的结论是，hGC33增加了SFB-NP对HCC细胞的靶向。hGC33-SFB-NP通过阻断Wnt途径和Ras / Raf / MAPK途径协同抑制HCC进程。