Issue 30, 2024

Iron oxide nanozymes enhanced by ascorbic acid for macrophage-based cancer therapy

Abstract

In recent years, using pharmacological ascorbic acid has emerged as a promising therapeutic approach in cancer treatment, owing to its capacity to induce extracellular hydrogen peroxide (H2O2) production in solid tumors. The H2O2 is then converted into cytotoxic hydroxyl free radicals (HO˙) by redox-active Fe2+ inside cells. However, the high dosage of ascorbic acid required for efficacy is hampered by adverse effects such as kidney stone formation. In a recent study, we demonstrated the efficient catalytic conversion of H2O2 to HO˙ by wüstite (Fe1−xO) nanoparticles (WNPs) through a heterogenous Fenton reaction. Here, we explore whether WNPs can enhance the therapeutic potential of ascorbic acid, thus mitigating its dose-related limitations. Our findings reveal distinct pH dependencies for WNPs and ascorbic acid in the Fenton reaction and H2O2 generation, respectively. Importantly, WNPs exhibit the capability to either impede or enhance the cytotoxic effect of ascorbic acid, depending on the spatial segregation of the two reagents by cellular compartments. Furthermore, our study demonstrates that treatment with ascorbic acid promotes the polarization of WNP-loaded macrophages toward a pro-inflammatory M1 phenotype, significantly suppressing the growth of 4T1 breast cancer cells. This study highlights the importance of orchestrating the interplay between ascorbic acid and nanozymes in cancer therapy and presents a novel macrophage-based cell therapy approach.

Graphical abstract: Iron oxide nanozymes enhanced by ascorbic acid for macrophage-based cancer therapy

Supplementary files

Article information

Article type
Paper
Submitted
18 mar 2024
Accepted
11 jul 2024
First published
15 jul 2024
This article is Open Access
Creative Commons BY-NC license

Nanoscale, 2024,16, 14330-14338

Iron oxide nanozymes enhanced by ascorbic acid for macrophage-based cancer therapy

Z. Yi, X. Yang, Y. Liang and S. Tong, Nanoscale, 2024, 16, 14330 DOI: 10.1039/D4NR01208A

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