The advancing of polymeric core-shell ZnO nanocomposites containing 5-fluorouracil for improving anticancer activity in colorectal cancer

Naunyn Schmiedebergs Arch Pharmacol. 2024 Feb;397(2):899-911. doi: 10.1007/s00210-023-02643-x. Epub 2023 Aug 2.

Abstract

The study investigated the use of 5-fluorouracil-loaded ZnO nanocomposites (5-FU/Gd-ZnO NCs) as a potential treatment for cancer. 5-FU is a commonly used drug for cancer treatment but has undesirable side effects. The materials were characterized using various techniques, including PXRD, FTIR, FESEM, TEM, DLS, £-potential, and AFM. The data showed that the nanocomposites had a plate-like agglomeration with particle diameters ranging from 317.6 to 120.1 nm. The IC50 value of 5-FU-ZnO, which inhibits cell growth, was found to be 1.85 ppm. The effects of 5-FU-ZnO on inflammatory markers were also examined. While 5-FU increased the levels of TNF-a and IL-1b, the nanocomposites were able to reduce these levels. Additionally, the 5-FU/Gd-ZnO-NCs group showed an increase in thiol levels and a decrease in catalase and superoxide dismutase levels. Flow cytometry results showed that 5-FU, ZnO-NCs, and 5-FU/Gd-ZnO-NCs did not have any additive or synergistic effects on the suppression or eradication of cancer cells. In vivo, experiments showed that the 5-FU/Gd-ZnO NCs had similar necrotic characteristics and reduced fibrosis and collagen deposition compared to the free medication. The nanocomposites also exhibited higher antioxidative activity and lower inflammatory responses compared to the 5-FU group. It was shown that 5-FU/Gd-ZnO-NCs successfully inhibit cell proliferation. The in vivo results were comparable to those obtained with free 5-FU, suggesting the potential of these nanocomposites as therapeutic agents.

Keywords: 5-Fluorouracil; Colorectal cancer; Drug delivery; Polymer-ZnO nanocomposites.

MeSH terms

  • Antioxidants
  • Colorectal Neoplasms* / drug therapy
  • Fluorouracil / pharmacology
  • Humans
  • Nanocomposites*
  • Zinc Oxide*

Substances

  • Fluorouracil
  • Zinc Oxide
  • Antioxidants