In the realm of biomedical research, the need for bioactive molecular agents that not only offer real-time monitoring but also simultaneous inhibition of oxidative stress and inflammation is of utmost importance. Traditional imaging methods, such as computed tomography and magnetic resonance imaging, have limitations when it comes to precise diagnostics and real-time analysis. To bridge this gap, Huizhen Ma and a multidisciplinary research team at Tianjin University China have developed atomically precise gold clusters with strong near-infrared II (NIRII) fluorescence, showcasing potent enzyme-mimetic activities. This breakthrough technology opens up new possibilities in the field of translational medicine and offers promise for advanced diagnostics and interventions.
Overcoming the Limitations
The bioactivity of most NIRII fluorophores is limited, hindering the achievement of strong fluorescence and high catalytic activities. The lack of free electrons in the method has been a major challenge. However, Ma et al. have successfully overcome this limitation by using atomic engineering to develop gold-copper clusters (Au21Cu1) with enhanced antioxidant properties. These clusters exhibit a 90-fold catalase-like activity and 3-fold higher superoxide dismutase-like activity compared to gold clusters alone. Furthermore, they can be effectively cleared through the kidney, making them suitable for monitoring cisplatin-induced renal injury in real-time using near-infrared light-sheet microscopy.
A Promising Approach
The engineered gold-copper clusters demonstrate tremendous potential in preventing oxidative stress and inflammation in both the kidney and brain. This is particularly crucial when considering the side effects that arise from treatments like cisplatin, an anticancer drug. Cisplatin, while effective against cancer, can lead to acute kidney injury and neurotoxicity due to its ability to induce oxidative stress and inflammation. Real-time monitoring of these conditions is essential for early diagnosis and intervention.
Real-Time Monitoring with NIR-II Imaging
The method of near-infrared II (NIR-II) imaging offers high tissue penetration depth and signal-to-noise ratio, making it an ideal tool for monitoring cancer pathogenesis and pathological evolution. By harnessing the power of biocatalytic NIR-II molecular agents, researchers can now conduct real-time monitoring of pathological processes and molecular mechanisms of treatment. Early intervention for oxidative stress-based diseases becomes possible through precise diagnostics and analysis.
Achieving Atomic Precision
To create stable structures with enhanced bioactivity, Ma et al. utilized atomic precision engineering. They prepared gold clusters (Au22) and purified them to achieve an ultrasmall size, allowing for efficient renal filtration. The resulting gold-copper clusters exhibited excellent photostability, water solubility, and homogeneity. By incorporating atomic engineering, the researchers could modify the clusters and obtain optical absorption spectra of the doped clusters. The addition of a single copper atom active site led to significantly higher catalytic activity, with the doped clusters demonstrating 90 times the catalytic activity of pure gold clusters.
Unveiling the Impact of NIR-II Properties
This groundbreaking work sheds light on the impact of clusters with NIR-II properties, a crucial aspect in the field of life sciences. The engineered bioactive NIR-II molecules provide a platform for understanding mechanisms and offer urgent opportunities for further research. Through density functional theory calculations, Ma et al. comprehensively examined the gold clusters, providing valuable insights into their properties and potential applications.
To evaluate the effectiveness of gold-copper clusters for real-time kidney monitoring, the research team conducted experiments on mice. By administering cisplatin, they were able to induce acute kidney injury and observe the subsequent impairment of kidney function and nervous system influence. The gold clusters accumulated in the kidney, allowing for localization and monitoring. Cytotoxicity tests confirmed the clusters’ ability to regulate oxidative stress and induce favorable biological activities without toxicity.
Cisplatin-induced injury in the kidney and brain is closely linked to oxidative stress and inflammation. The toxic effects of cisplatin are of great concern, making it imperative to develop innovative approaches to mitigate its side effects. Through atomic engineering, the gold-copper clusters developed by Ma et al. exhibit ultrahigh enzymatic mimicry, providing enhanced antioxidant activity. The biological experiments conducted by the research team demonstrated the clusters’ potential to inhibit both oxidative stress and inflammation in the kidney-brain axis during kidney disease.
A Game-Changing Tool with Biosafety and Multifunctionality
In addition to their catalytic and fluorescence properties, the gold-copper clusters possess efficient biosafety and multifunctionality. The clusters can undergo renal clearance without inducing toxicity, even at high doses. This enables their potential utilization in real-time imaging and early intervention during acute kidney injury. The gold-copper clusters have the potential for successful translation from the laboratory to clinical applications, truly revolutionizing the field of medicine.
Huizhen Ma and her team’s groundbreaking research on gold-copper clusters with strong NIR-II fluorescence and potent enzyme-mimetic activities represents a significant leap forward in real-time monitoring and intervention. By addressing the limitations of bioactivity in NIRII fluorophores and leveraging atomic engineering, these clusters offer tremendous potential in inhibiting oxidative stress and inflammation while enabling real-time diagnostics. The development of biocatalytic NIR-II molecular agents and their applications in monitoring pathological processes hold promise for improving early intervention strategies. With further advancements and research, this technology may transform the way we diagnose and treat disease, leading to a healthier and more informed future.
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