Bio-based protocatechuic acid-anchored multimetallic nanoreactors: Green construction, redox-cycling properties, and biomedical potential

Wanmei Zhou; Litao Wang; Chengdong Nie; Zixin Wang; Qi Gu; Haiting Tian; Chenlu Wang; Thomas Efferth; Yujie Fu

doi:10.1016/j.jobab.2026.100298

Volume 11 Issue 5

Oct. 2026

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Wanmei Zhou, Litao Wang, Chengdong Nie, Zixin Wang, Qi Gu, Haiting Tian, Chenlu Wang, Thomas Efferth, Yujie Fu. Bio-based protocatechuic acid-anchored multimetallic nanoreactors: Green construction, redox-cycling properties, and biomedical potential[J]. Journal of Bioresources and Bioproducts, 2026, 11(5): 100298. doi: 10.1016/j.jobab.2026.100298

Citation:

Wanmei Zhou, Litao Wang, Chengdong Nie, Zixin Wang, Qi Gu, Haiting Tian, Chenlu Wang, Thomas Efferth, Yujie Fu. Bio-based protocatechuic acid-anchored multimetallic nanoreactors: Green construction, redox-cycling properties, and biomedical potential[J]. Journal of Bioresources and Bioproducts, 2026, 11(5): 100298. doi: 10.1016/j.jobab.2026.100298

Citation:

Wanmei Zhou, Litao Wang, Chengdong Nie, Zixin Wang, Qi Gu, Haiting Tian, Chenlu Wang, Thomas Efferth, Yujie Fu. Bio-based protocatechuic acid-anchored multimetallic nanoreactors: Green construction, redox-cycling properties, and biomedical potential[J]. Journal of Bioresources and Bioproducts, 2026, 11(5): 100298. doi: 10.1016/j.jobab.2026.100298

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Bio-based protocatechuic acid-anchored multimetallic nanoreactors: Green construction, redox-cycling properties, and biomedical potential

doi: 10.1016/j.jobab.2026.100298

Wanmei Zhou^a,b,
Litao Wang^a,b,
Chengdong Nie^e,
Zixin Wang^f,g,
Qi Gu^a,b,
Haiting Tian^a,b,
Chenlu Wang^a,b,
Thomas Efferth^h,
Yujie Fu^{a,b,c,d
,
,}

a The College of Forestry, Beijing Forestry University, Beijing 100083, China;
b State Key Laboratory of Efficient Production of Forest Resources, Beijing Forestry University, Beijing 100083, China;
c Beijing Key Laboratory of Efficient Synthesis of Plant Secondary Metabolites, Beijing Forestry University, Beijing 100083, China;
d Ecological Observation and Research Station of Heilongjiang Sanjiang Plain Wetlands, National Forestry and Grassland Administration, Shuangyashan 155600, China;
e College of Chemistry, Chemical Engineering and Resource Utilization, Northeast Forestry University, Harbin 150040, China;
f Institute of Integration of Traditional and Western Medicine, Guangzhou Medical University, Guangzhou 511436, China;
g Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou 510006, China;
h Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Mainz 55128, Germany

Funds:

This study was financially supported by the National Key R&D Program of China (Grant No. 2022YFD2200602), the National Natural Science Foundation of China (No. 32271805), the Science and Technology Innovation Program of Xiongan New Area (No. 2025XAGG0057), the S&T Program of Xiongan New Area (No. XA202501102004K), and the 5·5 Engineering Research & Innovation Team Project of Beijing Forestry University (No. BLRC2023A01).

Received Date: 2026-03-16
Accepted Date: 2026-07-24
Rev Recd Date: 2026-07-06

Available Online: 2026-11-03

Publish Date: 2026-09-01

Abstract

Abstract

Tumor cells often develop reductive adaptations that decrease the effectiveness of reactive oxygen species (ROS)-dependent treatments, prompting a need for catalytic platforms that sustainably amplify redox stress. In this work, we constructed a bio-based protocatechuic acid (PCA)-anchored multimetallic Fe-based metal-organic framework (Fe-MOF) nanoreactor with magnetic resonance imaging (MRI) capability and redox-activated therapeutic potential. Combining the PCA-coordinated Fe²⁺/Fe³⁺ framework with Cu⁺/Cu²⁺ redox cycling and ultrasmall Au domains, this redox network formed a tightly interconnected Fe/Cu/Au catalytic system that supported Fenton-type conversion of H₂O₂ into ·OH, glutathione (GSH) depletion, and enhanced oxidative stress in tumor environments. The addition of the natural compound brazilin (BRA) promoted apoptosis and enhanced the sensitivity of tumor cells to ferroptosis. Surface coating with homotypic 4T1 cell membranes enabled tumor homing and facilitated BRA release within tumors. Mechanistically, the nanoreactor perturbed cellular redox regulation across multiple metabolic pathways, including reduced expression of cytochrome c oxidase subunit 4 isoform 1 (COX4I1), serine hydroxymethyltransferase 2 (SHMT2), and dihydroorotate dehydrogenase (DHODH), suppression of the glutathione peroxidase 4 (GPX4)-solute carrier family 7 member 11 (SLC7A11) antioxidant response, and acyl-CoA synthetase long-chain family member 4 (ACSL4)-mediated lipid remodeling. In general, PCA-ligated Fe-MOF sequentially modified with Au, Cu, BRA, and 4T1 cell membranes (FP@ACBM) enhanced ROS accumulation, promoted lipid peroxidation, and induced apoptosis, thus producing antitumor effects. At the same time, it enabled stable longitudinal relaxation time (T₁)-weighted MRI contrast enhancement. Overall, this bio-based phenolic ligand-assembled mixed-valence Fe-MOF platform provides a versatile strategy for constructing redox-cycling nanomaterials with promising biomedical applications.
- Breast cancer,
- Bio-based,
- Fe based metal-organic framework,
- Nanoreactor,
- Redox cycling,
- Ferroptosis

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References(68)

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