Albumin hybrid nanoparticles loaded with tyrosine kinase A inhibitor GNF-5837 for targeted inhibition of breast cancer cell growth and invasion

作者：Shargh Vahid Heravi; Hondermarck Hubert; Liang Mingtao

来源：International Journal of Pharmaceutics, 2016, 515(1-2): 527-534.

DOI：10.1016/j.ijpharm.2016.10.057

• Albumin hybrid nanoparticles
• TrkA inhibitor
• Breast cancer
• Targeted therapy

Novel albumin hybrid nanoparticles (Alb-HNPs) loaded with tyrosine kinase A (TrkA) inhibitor GNF-5837 were prepared and evaluated for antineoplastic efficacy in a panel of breast cancer cell lines. The nanomedicines (GNF-Alb-HNPs, hydrodynamic diameter similar to 150 nm) were formed through a unique polyelectrolyte complexation process where albumin and GNF-5837 were encapsulated by a stabilizing layer of oppositely charged chitosan and dextran sulfate polysaccharides. GNF-Alb-HNPs showed an excellent colloidal stability and a sustained drug release over more than 24 h. We found that these nanomedicines inhibited TrkA phosphorylation and downstream mitogen-activated protein kinase (MAPK) signaling in breast cancer cells specifically, resulting in anti-proliferative and pro-apoptotic effects. Moreover, the migration and invasion activities of cancer cells were dramatically suppressed and the inhibitory effects were much more prominent with GNF-Alb-HNPS than the drug alone. These results show that the GNF-Alb-HNPs may represent a novel approach for targeted breast cancer therapy.

• 出版日期2016-12-30