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

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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.

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The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Authors and Affiliations

  1. Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran

    Samaneh Mohammadian & Parvaneh Maghami

  2. Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Amir Avan & Majid Khazaei

  3. Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Amir Avan

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  1. Samaneh Mohammadian
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Contributions

Samaneh Mohammadian did all the lab experiments and wrote the manuscript with support from Parvaneh Maghami, Amir Avan, and Majid Khazaei. Parvaneh Maghami supervised the project. Amir Avan and Majid Khazaei contributed to the interpretation of the cellular section and in vivo part, respectively. All authors reviewed the manuscript. The authors declare that all data were generated in-house and that no paper mill was used.

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Correspondence to Parvaneh Maghami.

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Mohammadian, S., Avan, A., Khazaei, M. et al. The advancing of polymeric core–shell ZnO nanocomposites containing 5-fluorouracil for improving anticancer activity in colorectal cancer. Naunyn-Schmiedeberg's Arch Pharmacol 397, 899–911 (2024). https://doi.org/10.1007/s00210-023-02643-x

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