Lignin-graft-PLGA drug-delivery system improves efficacy of MEK1/2 inhibitors in triple-negative breast cancer cell line

Nanomedicine (Lond). 2020 Apr;15(10):981-1000. doi: 10.2217/nnm-2020-0010. Epub 2020 Apr 2.

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.

Keywords: breast cancer; drug delivery; lignin; nanoparticle; targeted therapies; triple-negative.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Cell Line, Tumor
  • Drug Delivery Systems*
  • Humans
  • Lignin
  • MAP Kinase Kinase 1 / antagonists & inhibitors
  • MAP Kinase Kinase 2 / antagonists & inhibitors
  • Nanoparticles*
  • Polyglycolic Acid / therapeutic use
  • Polylactic Acid-Polyglycolic Acid Copolymer*
  • Triple Negative Breast Neoplasms* / drug therapy

Substances

  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lignin
  • MAP2K2 protein, human
  • MAP Kinase Kinase 1
  • MAP Kinase Kinase 2