Precise regulation of reactive oxygen species (ROS) is essential for effective infected wound healing, where a delicate balance between antibacterial activity and tissue protection must be maintained. Excessive ROS can damage healthy tissues and delay regeneration, while insufficient ROS fails to eliminate pathogenic bacteria. Addressing this challenge, researchers have developed a pH-responsive bifunctional nanozyme capable of dynamically regulating ROS levels in response to the wound microenvironment, offering a promising inorganic catalytic strategy for infected wound therapy.
A research team from the Beijing University of Chemical Technology (BUCT), China, led by Guolie Xiang, reports the design of a sub-nanoscale 12-phosphotungstic acid (PTA) cluster-functionalized Fe3O4 nanozyme for biomedical applications. Zohaib Rana, a member of the research team, contributed to the development and evaluation of the inorganic nanozyme system. The study integrates concepts from industrial chemistry and energy chemistry to advance inorganic catalyst platforms for bioapplications.
The team published their findings in Nano Research , where they systematically investigated the structure, catalytic behavior, and biological performance of the Fe3O4-PTA nanozyme in both in vitro and in vivo models.
Unlike conventional wound-healing strategies that focus primarily on ROS production, the Fe3O4-PTA nanozyme exhibits pH-dependent bifunctional catalytic behavior. In the acidic microenvironment characteristic of infected wounds, the nanozyme displays strong peroxidase-like activity, catalyzing hydrogen peroxide to generate highly reactive ROS that effectively disrupt bacterial membranes and induce bacterial death. As the wound environment gradually shifts toward physiological pH during healing, the nanozyme transitions into a ROS-scavenging mode, eliminating excess ROS and mitigating oxidative stress.
This dynamic catalytic switch enables the nanozyme to simultaneously achieve potent antibacterial efficacy and protection of surrounding healthy tissues, promoting accelerated wound closure and tissue regeneration. Kinetic analyses demonstrated high intrinsic catalytic activity toward typical peroxidase substrates, while antioxidant assays confirmed efficient scavenging of multiple ROS species, including hydroxyl radicals and hydrogen peroxide.
In vivo infected wound healing experiments further validated the therapeutic potential of the Fe3O4-PTA nanozyme. Compared with Fe3O4 alone, the PTA-functionalized nanozyme significantly enhanced wound closure, reduced inflammatory responses, and improved tissue remodeling, highlighting the critical role of sub-nanoscale cluster engineering in regulating nanozyme function.
"Our work demonstrates that inorganic catalyst-based nanozymes can be rationally engineered to achieve precise redox regulation in complex biological environments," said Guolei Xiang, lead author and first author Zohaib Rana of the study. "By integrating ROS generation and scavenging into a single pH-responsive system, we provide a new strategy for treating infected wounds while avoiding the risks associated with ROS overproduction."
The researchers emphasize that this study represents an important step toward expanding the application of inorganic nanozymes, offering a versatile platform for managing ROS-related pathological conditions. The design concept may also be extended to other biomedical scenarios where redox homeostasis plays a critical role, including inflammation control and tissue repair.
This work was supported by National Natural Science Foundation of China (Nos. 22575013, 82271012), which support fundamental and applied research on functional inorganic catalysts and nanozyme-based bio-applications. These projects aim to advance the development of catalytic materials for healthcare and energy-related technologies.
DOI Link:
https://doi.org/10.26599/NR.2026.94908373
About Nano Research
Nano Research is a peer-reviewed, open access, international and interdisciplinary research journal, sponsored by Tsinghua University and the Chinese Chemical Society, published by Tsinghua University Press on the platform SciOpen. It publishes original high-quality research and significant review articles on all aspects of nanoscience and nanotechnology, ranging from basic aspects of the science of nanoscale materials to practical applications of such materials. After 18 years of development, it has become one of the most influential academic journals in the nano field. Nano Research has published more than 1,000 papers every year from 2022, with its cumulative count surpassing 8,000 articles. In 2025 InCites Journal Citation Reports, its 2025 IF is 9.4 (8.3, 5 years), and it continues to be the Q1 area among the four subject classifications. Nano Research Award, established by Nano Research together with TUP and Springer Nature in 2013, and Nano Research Young Innovators (NR45) Awards, established by Nano Research in 2018, have become international academic awards with global influence.
