Bio-based protocatechuic acid-anchored multimetallic nanoreactors: Green construction, redox-cycling properties, and biomedical potential
Year: 2026
Type: article
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 Fe 2+ /Fe 3+ framework with Cu + /Cu 2+ redox cycling and ultrasmall Au domains, this redox network formed a tightly interconnected Fe/Cu/Au catalytic system that supported Fenton-type conversion of H 2 O 2 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 ( T 1 )-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.
Language: English
Subfield: Biomedical Engineering
Field: Engineering
Domain: Physical Sciences
Open Access status: diamond
Funders: Civil Engineering Research and Innovation for Sustainability, Government of Pudong New Area, National Natural Science Foundation of China, Beijing Information Science and Technology University, Beijing Forestry University, National Key Research and Development Program of China, National Key Research and Development Program of China Stem Cell and Translational Research
OpenAlex ID: W7204915581