Bio-Based Fe-MOF nanoreactor builds a redox-cycling strategy for breast cancer therapy

Chemodynamic therapy uses metal-mediated reactions to convert endogenous hydrogen peroxide into highly reactive hydroxyl radicals inside tumors. However, the approach can be limited by insufficient H₂O₂, rapid antioxidant removal of reactive species and inefficient regeneration of catalytic metal ions. These limitations have prompted interest in nanoreactors capable of sustaining redox reactions within the tumor microenvironment.

In a study published in the Journal of Bioresources and Bioproducts, researchers developed a bio-based Fe-MOF nanoreactor using protocatechuic acid (PCA) as a natural redox-active ligand. The PCA–Fe(II/III) framework formed a flower-cluster-like structure and provided a catalytic scaffold for subsequent functionalization. Ultrasmall Au nanoparticles were introduced to facilitate electron transfer and oxygen reduction, while Cu(I)/Cu(II) species established a multimetallic Fe/Cu/Au redox cycle.

The researchers further loaded brazilin, a plant-derived phenolic compound with reported antitumor activity, and coated the particles with 4T1 breast cancer cell membranes. The membrane coating was intended to promote homotypic interactions with tumor cells, while the Fe-containing framework also provided T1-weighted magnetic resonance contrast for imaging. The resulting construct was designated FP@ACBM.

The multimetallic architecture was designed to address several barriers to conventional chemodynamic therapy simultaneously. Au promoted local H₂O₂ generation from oxygen, while Fe and Cu participated in Fenton-like reactions to produce hydroxyl radicals. At the same time, intracellular glutathione reduced oxidized metal species and was consumed during the redox cycle, helping sustain oxidative stress. In cultured 4T1 cells, FP@ACBM produced the strongest ROS response among the tested formulations and substantially increased apoptosis, lipid peroxidation and disruption of cellular redox balance.

The effects were also observed in vivo. After 15 days of treatment in 4T1 tumor-bearing mice, FP@ACBM produced an average tumor weight of 0.20 g and an approximately 80% tumor inhibition rate compared with the control group. No obvious differences in body weight were observed among treatment groups during the experiment. Tissue analysis further showed increased iron accumulation, reduced GPX4 and SLC7A11 expression, and evidence of lipid oxidative damage.

The study presents a multifunctional nanoplatform that combines natural-ligand chemistry with multimetallic redox catalysis, biomimetic targeting and MRI visibility. While further studies will be needed to evaluate safety, pharmacokinetics and therapeutic performance beyond the reported animal model, the results demonstrate how bio-based components can be incorporated into increasingly complex catalytic nanomaterials for biomedical research.

See the article:

DOI

https://doi.org/10.1016/j.jobab.2026.100298

Original Source URL

https://www.sciencedirect.com/science/article/pii/S2369969826000708

Journal

Journal of Bioresources and Bioproducts