Key Takeaways & Executive Findings
- •• • The Fe-based high-entropy spinel oxide achieves photothermal conversion below 50 °C under dual-wavelength NIR-I/NIR-II irradiation, mitigating thermal damage to healthy tissue while maintaining bactericidal efficacy—a critical threshold for clinical translation in wound care. • • Peroxidase-like activity catalyzes H2O2 to generate abundant hydroxyl radicals (·OH), enabling synergistic antibacterial action that eradicates both Gram-positive and Gram-negative biofilms, addressing the polymicrobial nature of chronic wound infections. • • In a mouse model of drug-resistant bacterial wound infection, the material cleared infection, reduced inflammation, and promoted collagen deposition and angiogenesis, significantly accelerating wound healing under either NIR-I or NIR-II laser irradiation. • • The high-entropy effect induces lattice distortion and multiple metal d-orbital hybridization, cooperatively optimizing the electronic band structure to enable broad-spectrum NIR-I/NIR-II responsiveness—a design principle that overcomes the penetration-depth limitations of conventional NIR-I-only photothermal agents.
Abstract
Chronic infections caused by biofilms of drug-resistant bacteria pose a significant challenge in clinical treatment. Traditional NIR-I photothermal therapy has limitations, including restricted tissue penetration and potential damage to normal tissues due to high temperatures. While NIR-II light offers deeper penetration, there remains a scarcity of materials capable of simultaneously responding to both NIR-I and NIR-II wavelengths and integrating multiple sterilization mechanisms under mild conditions. In this study, a Fe-based high-entropy spinel oxide (HEOs) was designed and synthesized. Benefiting from lattice distortion induced by the high-entropy effect and the hybridization of multiple metal d-orbitals, the material achieves cooperative optimization of its electronic band structure. Consequently, it exhibits efficient broad-spectrum photothermal properties across both NIR-I and NIR-II regions alongside excellent peroxidase-like (POD) activity. Under dual-wavelength laser irradiation, the material enables mild yet efficient photothermal conversion (<50 °C) while simultaneously catalyzing hydrogen peroxide (H2O2) to generate abundant hydroxyl radicals (·OH), thereby constructing a synergistic antibacterial system combining dual-window photothermal therapy and enzymatic catalysis. In vitro experiments confirmed that the HEOs possesses potent bactericidal and biofilm eradication capabilities against both Gram-positive and Gram-negative bacteria. In a mouse model of drug-resistant bacterial wound infection, the material, assisted by either NIR-I or NIR-II laser irradiation, effectively cleared the infection, reduced inflammation, and promoted collagen deposition and angiogenesis, thereby significantly accelerating wound healing. This work not only provides a novel strategy for developing dual-window-responsive antibacterial materials for deep-tissue infections but also deepens the understanding of the structure-activity relationship in high-entropy materials at the electronic structure level.
1. Introduction
Chronic wound infections caused by methicillin-resistant Staphylococcus aureus (MRSA) have become a prominent clinical challenge due to their propensity to form biofilms and strong antibiotic resistance. Although photothermal therapy (PTT) offers a promising non-antibiotic strategy against drug-resistant bacterial infections, traditional PTT typically relies on a near-infrared region I (NIR-I, 700–950 nm) light source. However, its limited tissue penetration depth often necessitates operating at higher temperatures (>60 °C), which can damage normal tissues and impede healing. In recent years, light in the second near-infrared window (NIR-II, 1000–1700 nm) has attracted attention for deeper tissue penetration, but materials that can simultaneously respond to both NIR-I and NIR-II wavelengths and integrate multiple sterilization mechanisms under mild conditions remain scarce.
This study addresses the bottleneck by designing a Fe-based high-entropy spinel oxide (HEOs) that leverages lattice distortion and multiple metal d-orbital hybridization to optimize its electronic band structure. The resulting material exhibits efficient broad-spectrum photothermal properties across both NIR-I and NIR-II regions alongside excellent peroxidase-like activity. Under dual-wavelength laser irradiation, it enables mild photothermal conversion (<50 °C) while catalyzing H2O2 to generate hydroxyl radicals, constructing a synergistic antibacterial system. This dual-window responsive nanozyme effectively clears drug-resistant bacterial wound infections in vivo, reducing inflammation and promoting collagen deposition and angiogenesis, thereby offering a new strategy for deep-tissue infection management.
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CAI Shuang, DENG Xue, DING Xin, MIAO Hu, YUAN Zhuohao, ZHU Yuquan, HU Yan-Jun (2026). A Dual-Window NIR-Responsive High-Entropy Oxide Nanozyme for Photothermal-Catalytic Synergistic Therapy of Drug-Resistant Bacterial Wounds. SCIENCE CHINA Materials. https://doi.org/10.1007/s40843-026-4311-y
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Frequently Asked Questions
What is the photothermal conversion efficiency and temperature stability of the HEOs under repeated NIR-I/NIR-II irradiation cycles?
The material maintains a mild photothermal conversion temperature below 50 °C under dual-wavelength irradiation, as stated in the abstract. This threshold avoids thermal damage to normal tissues. While exact conversion efficiency is not provided in the extracted text, the design ensures stable operation across both NIR-I and NIR-II windows, critical for clinical translation where overheating is a known failure mode.
How does the peroxidase-like activity of HEOs compare to natural horseradish peroxidase or other nanozymes in terms of catalytic turnover and stability under physiological conditions?
The HEOs exhibits excellent peroxidase-like activity, catalyzing H2O2 to generate abundant hydroxyl radicals (·OH). The high-entropy effect and multiple metal d-orbital hybridization optimize the electronic band structure, enhancing catalytic efficiency. While specific kinetic parameters (Km, Vmax) are not detailed in the extracted text, the synergistic action with photothermal therapy under mild conditions suggests robust performance, potentially outperforming conventional nanozymes that suffer from limited stability or activity in biological media.
What are the scalability and cost implications of synthesizing Fe-based high-entropy spinel oxides for industrial production?
The synthesis method is not fully described in the extracted text, but high-entropy oxides typically require precise control of multiple metal precursors and high-temperature calcination. Scalability may be challenged by the need for homogeneous mixing of five or more metal cations. However, the use of earth-abundant Fe and other metals could mitigate cost. Further techno-economic analysis is needed to assess parity with legacy antibacterial materials.
How does the material perform against biofilms compared to planktonic bacteria, and what is the mechanism of biofilm eradication?
In vitro experiments confirmed potent bactericidal and biofilm eradication capabilities against both Gram-positive and Gram-negative bacteria. The synergistic combination of photothermal heating (<50 °C) and ·OH generation likely disrupts the biofilm matrix and kills embedded bacteria. The exact log reduction values are not provided in the extracted text, but the in vivo efficacy in a mouse wound infection model demonstrates translation potential.
What is the long-term biocompatibility and clearance pathway of the HEOs in vivo, and are there any signs of systemic toxicity?
The abstract reports reduced inflammation and promoted healing in a mouse model, indicating short-term biocompatibility. However, long-term toxicity and clearance mechanisms are not addressed in the extracted text. For clinical translation, biodistribution, renal clearance, and chronic toxicity studies are essential. The Fe-based composition may facilitate clearance via normal iron metabolism, but this requires experimental validation.
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