Anhorn Marion G, Wagner Sylvia, Kreuter Jörg, Langer Klaus, von Briesen Hagen
Institute of Pharmaceutical Technology, Biocenter of Johann Wolfgang Goethe-University, 60438 Frankfurt/Main, Germany.
Bioconjug Chem. 2008 Dec;19(12):2321-31. doi: 10.1021/bc8002452.
Specific targeting of tumor cells to achieve higher drug levels in tumor tissue and to overcome cardiotoxic and other secondary effects is the major goal in cancer therapy. With trastuzumab as a humanized monoclonal antibody binding, the HER2 receptor specific targeting is possible. In the present study, target-oriented nanoparticles based on biodegradable human serum albumin (HSA) loaded with cytostatic drug doxorubicin were developed. The surface of the nanoparticles was modified by covalent attachment of trastuzumab. HER2 overexpressing breast cancer cells showed a good cellular binding and uptake of these nanoparticles. The specific transport of the cytostatic drug doxorubicin with this nanoparticulate formulation into the HER2 overexpressing breast cancer cells, their release, and biological activity was demonstrated. The results indicate that these cell-type specific drug-loaded nanoparticles could achieve an improvement in cancer therapy. To our knowledge, this is the first study demonstrating a specific trastuzumab-based targeting of HER2 overexpressing breast cancer cells with doxorubicin-loaded nanoparticles.
在癌症治疗中，特异性靶向肿瘤细胞以在肿瘤组织中实现更高的药物水平，并克服心脏毒性和其他副作用是主要目标。使用曲妥珠单抗这种人源化单克隆抗体进行结合，可以实现对HER2受体的特异性靶向。在本研究中，开发了基于可生物降解的人血清白蛋白（HSA）并负载细胞毒性药物阿霉素的靶向纳米颗粒。通过曲妥珠单抗的共价连接对纳米颗粒表面进行了修饰。HER2过表达的乳腺癌细胞对这些纳米颗粒表现出良好的细胞结合和摄取。证明了细胞毒性药物阿霉素通过这种纳米颗粒制剂特异性转运到HER2过表达的乳腺癌细胞中、其释放以及生物活性。结果表明，这些细胞类型特异性载药纳米颗粒可以改善癌症治疗。据我们所知，这是第一项证明基于曲妥珠单抗的负载阿霉素纳米颗粒对HER2过表达的乳腺癌细胞进行特异性靶向的研究。
