Targeted delivery of chrysin and 5-fluorouracil on MDA-MB-231 cancer cells by a peptide-functionalized L-DOPA-imprinted polymer.

Abstract

Triple-negative breast cancer (TNBC) is a very aggressive and deadly form of breast cancer for which chemotherapy is the only systemic treatment option. Therefore, novel and more effective targeted or combined therapies, such as specific drug delivery systems that selectively target cancer cells, have received much attention. This research aimed to investigate the effect of targeted delivery of chrysin (CH) and 5-fluorouracil (5FU) using polymer nanoparticles on MDA-MB-231 cells. In this regard, CH and 5FU were individually used as the template to polymerize L-DOPA on the surface of silica nanoparticles. Then, a CD138-targeting peptide was designed for the first time and immobilized on the surface of the polymeric nanocomposite to target TNBC. The results showed that poly(L-DOPA)-CH-peptide and poly(L-DOPA)-5FU-peptide are selective for MDA-MB-231 cells and deliver drugs to them in a targeted manner. In this study, peptide-containing nanocomposites targeting CD138 were more successful in reducing cell proliferation than peptide-free nanocomposites. Also, they increased apoptosis and cell cycle arrest in MDA-MB-231 cancer cells in vitro. The effective and targeted delivery of CH and 5FU to MDA-MB-231 cancer cells by the designed interference peptide in this study can promise an effective treatment method for inhibiting the growth and progression of cancer. However, animal studies are needed to understand the efficacy of the interfering peptide and the final designed construct.