A convergent synthetic platform for polymeric nanoparticle for the treatment of combination colorectal cancer therapy

J Biomater Sci Polym Ed. 2021 Oct;32(14):1835-1848. doi: 10.1080/09205063.2021.1941556. Epub 2021 Jul 9.

Abstract

In biomaterials and drug delivery, the development of polymeric therapies capable of the synchronized release of several therapeutic agents remains an important challenge. In this article, we describe the development of polymeric nanoparticles (PNPs) with precise molar ratios of Curcumin (CUR) and Methotrexate (MEX). The highly symmetric synthetic approach allows for the development of novel NPs-based combination therapeutic strategies for colorectal cancer. The fabricated CUR/MEX@PNPs were confirmed by transmission microscopy (TEM) and the size and polydispersity index were assessed through the dynamic light scattering (DLS). CUR and MEX were released slowly from the drug delivery without any burst impact. Furthermore, CUR/MEX@PNPs exhibited dose-responsive cytotoxic effects in CL40 and SW1417 cells, with a greater cell death ratio than that of free drugs. The drugs-loaded polymeric nanomaterials were more easily taken up by cancer cells in vitro, according to the cellular uptake analysis. The apoptotic features were confirmed by various fluorescence staining assay. The results of the fluorescent assay reveal that the nanomaterials remarkably induce apoptosis in colorectal cancer cells. Further, the apoptosis cell death mechanism was displayed that these nanomaterials significantly induce apoptosis in the targeted cancer cells. Overall, the current investigation confirmed that CUR/MEX@PNPs could be used to successfully combat colorectal cancers in the immediate future.HighlightsWe have developed the Curcumin (CUR) and Methotrexate (MEX) encapsulated polymeric nanoparticles (CUR/MEX@PNPs).CUR/MEX@PNPs confirmed by the various analytical methods.CUR/MEX@PNPs enhanced the in vitro proliferation against the colorectal cancer cells.Biochemical analysis results reveals that CUR/MEX@PNPs induce apoptosis.The apoptosis was confirmed by Annexin-V-FITC and PI for flow cytometry.

Keywords: Combination therapy; apoptosis; colorectal cancer; curcumin; methotrexate (MEX).

MeSH terms

  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Cell Line, Tumor
  • Colorectal Neoplasms* / drug therapy
  • Curcumin* / pharmacology
  • Drug Carriers
  • Drug Delivery Systems
  • Humans
  • Nanoparticles*
  • Particle Size

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Curcumin