Lignin-Graft-Plga Drug-Delivery System Improves Efficacy of MEK1/2 Inhibitors in Triple-Negative Breast Cancer Cell Line

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.

Graphical abstract

Keywords::

• breast cancer
• drug delivery
• lignin
• nanoparticle
• targeted therapies
• triple-negative

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/nnm-2020-0010

Author contributions

The manuscript was written through contributions of all authors. All the authors have given approval to the final version of the manuscript.

Financial & competing interests disclosure

This work was supported by the National Science Foundation under NSF EPSCoR Track 2 RII, OIA 1632854; the USDA National Institute of Food and Agriculture, AFRI project #2017-07878; the USDA National Institute of Food and Agriculture, AFRI project #2018-07406; USDA-NIFA Hatch #1008750; and the National Science Foundation, CBET 1509713. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This work was supported by the National Science Foundation under NSF EPSCoR Track 2 RII, OIA 1632854; the USDA National Institute of Food and Agriculture, AFRI project #2017-07878; the USDA National Institute of Food and Agriculture, AFRI project #2018-07406; USDA-NIFA Hatch #1008750; and the National Science Foundation, CBET 1509713. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.