Lignin-Graft-Plga Drug-Delivery System Improves Efficacy of MEK1/2 Inhibitors in Triple-Negative Breast Cancer Cell Line
C. Ethan Byrne, Carlos E. Astete, Manibarathi Vaithiyanathan, Adam T. Melvin, Mahsa Moradipour, Stephen E. Rankin, Barbara L. Knutson, Cristina M. Sabliov, Elizabeth C. Martin
Abstract
Aim: Few targeted therapies are available for triple-negative breast cancer (TNBC) patients. Here, we propose a novel alkaline-lignin-conjugated-poly(lactic-co-glycolic acid) (L-PLGA) nanoparticle drug delivery system to improve the efficacy of targeted therapies. Materials & methods: L-PLGA nanoparticles (NPs) loaded with the MEK1/2 inhibitor GDC-0623 were characterized, tested in vitro on MDA-MB-231 TNBC cell line and compared with loaded PLGA NPs. Results: Loaded L-PLGA NPs were less than half the size of PLGA NPs, had slower drug release and improved the efficacy of GDC-0623 when tested in vitro. We demonstrated that GDC-0623 reversed epithelial-to-mesenchymal transition in TNBC. Conclusion: Our findings indicate that L-PLGA NPs are superior to PLGA NPs in delivering GDC-0623 to cancer cells for improved efficacy in vitro.