Tendinopathy is a degenerative disease involving tendons, primarily caused by degenerative changes in the collagen fibers within the tendon. Current treatment methods for tendinopathy are diverse, including non-surgical and surgical approaches. Non-surgical treatments mainly consist of rest and immobilization, physical therapy, pharmacological interventions, and traditional Chinese massage, aiming to alleviate pain, reduce inflammation, promote tendon repair, and restore function. For patients with severe conditions or those unresponsive to conservative treatments, surgical interventions such as excision of pathological tissues are considered. However, these treatments predominantly address symptom relief rather than curing tendinopathy, necessitating the development of more effective therapeutic strategies.
A collaborative research team from Nanjing University School of Medicine and Xuchang University School of Chemical Engineering and Materials Science has recently designed a highly efficient reactive oxygen species (ROS) biocatalyst—PtIrRuRhCu high-entropy alloy nanozymes (HEANZs)—for treating tendinopathy. These non-ionic block copolymer (polyvinylpyrrolidone)-coated PtIrRuRhCu HEANZs, with an average size of approximately 4.0 nm, exhibit excellent biocompatibility and multiple enzyme-like antioxidant activities, including peroxidase (POD), catalase (CAT), and superoxide dismutase (SOD)-like activities, enabling effective ROS scavenging.
The research team published their findings in Nano Research on April 11, 2025. The study concluded: "Significant ROS accumulation, reduced mitochondrial autophagy, and elevated ferroptosis levels were identified in tendinopathic tendon tissues. The PtIrRuRhCu nanozyme biocatalyst efficiently scavenges ROS and restores mitochondrial autophagy via the PGAM5/FUNDC1/GPX4 pathway, thereby alleviating ferroptosis and treating tendinopathy. PtIrRuRhCu demonstrates high biocompatibility, low cytotoxicity, and superior ROS clearance efficiency, offering a novel approach for clinical tendinopathy treatment with potential for clinical translation."
The PtIrRuRhCu HEANZs were synthesized via hydrothermal reduction of PtCl₄²⁻, RhCl₆²⁻, Ru³⁺, Ir³⁺, and Cu²⁺ in the presence of polyvinylpyrrolidone (PVP). The nanozymes exhibited well-dispersed spherical morphology with a lattice spacing of 0.241 nm, corresponding to the (111) crystal plane—a value intermediate between the (111) spacings of pure Pt (0.227 nm), Ir (0.221 nm), Ru (0.213 nm), Rh (0.220 nm), and Cu (0.208 nm). The average particle size was determined as 4.01 ± 0.09 nm. Energy-dispersive X-ray spectroscopy (EDS) mapping confirmed the atomic percentages of Pt, Ir, Ru, Rh, and Cu as 26.3%, 12.8%, 12.1%, 22.7%, and 26.1%, respectively, aligning with the compositional range of high-entropy alloys (5%-35%).
The POD-like activity of the HEANZs was demonstrated through accelerated oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of H₂O₂, evidenced by characteristic absorption peaks at 450 nm and 650 nm. The oxidation degree of TMB increased significantly with reaction time, and the initial reaction rate of the H₂O₂-TMB redox system exhibited concentration-dependent enhancement as the nanozyme concentration rose from 0.33 μM to 2.47 μM. CAT-like activity was validated via electron spin resonance (ESR)-based oximetry, where mixing HEANZs with H₂O₂ induced distinct ESR signal broadening and intensity reduction, confirming oxygen generation. Notably, 0.2 μM HEANZs triggered substantial oxygen production within 3 minutes, highlighting their exceptional CAT-like catalytic efficiency. Furthermore, the nanozymes demonstrated effective •OH scavenging capability—critical for neutralizing the most reactive oxygen species under physiological conditions. Collectively, the PtIrRuRhCu HEANZs exhibited superior antioxidant capacity and ROS regulatory potential for mitigating oxidative stress in biological systems.
The research team proposes that PtIrRuRhCu HEANZs may alleviate ferroptosis and treat tendinopathy by clearing ROS and restoring mitochondrial autophagy via the PGAM5/FUNDC1/GPX4 pathway. These findings provide a novel therapeutic strategy with significant clinical translation potential for tendinopathy management.
Contributors to the study include Lu Yang, Yang Shaojie, and Zhang Yibo from Nanjing University School of Medicine, along with Zhang Jiawei from Xuchang University School of Chemical Engineering and Materials Science.
This work received funding from multiple sources: the National Major Research Plan of NSFC (92368201), National Key Research and Development Project (2021YFA1201404), Major Project of NSFC (81991514), Jiangsu Province Medical Innovation Center of Orthopedic Surgery (CXZX202214), Jiangsu Provincial Key Medical Center Foundation, Jiangsu Provincial Medical Outstanding Talent Foundation, Jiangsu Provincial Medical Youth Talent Foundation, Jiangsu Provincial Key Medical Talent Foundation, and the Fundamental Research Funds for the Central Universities (14380493, 14380494).
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 7,000 articles. In 2024 InCites Journal Citation Reports, its 2024 IF is 9.0 (8.7, 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.
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