Recently, a research team led by Prof. WANG Hui from the Hefei Institutes of Physical Science of the Chinese Academy of Sciences, in collaboration with Prof. ZHAO Yanli' s group from Nanyang Technological University, constructed a novel urchin-like copper single-atom nanozyme (UCCSE) and revealed that needle length plays a critical role in enhancing cellular uptake and chemodynamic tumor therapy efficiency.
The research was published in ACS Nano.
Single-atom nanozymes, with well-defined atomic structure and highly efficient atom utilization, can efficiently decompose overexpressed hydrogen peroxide (H₂O₂) in the tumor microenvironment into highly cytotoxic hydroxyl radicals (•OH), thereby holding great promise for tumor chemodynamic therapy. However, their therapeutic performance is still hampered by limited cellular uptake and insufficient accumulation at tumor sites.
In this study, researchers employed a self-developed organic molecule carbonization-reduction strategy to synthesize a sea-urchin-like copper single-atom nanozyme (UCCSE) in a one-step solvothermal process. By precisely tuning the length of the surface needles, they were able to optimize the catalytic performance of UCCSE.
The UCCSE exhibited both peroxidase-like and glutathione peroxidase-like activities: it catalyzed endogenous H₂O₂ to continuously generate highly reactive •OH, while simultaneously consuming intracellular reductive glutathione, thereby suppressing •OH scavenging and amplifying oxidative stress to enhance chemodynamic therapy.
What' s more, researchers systematically investigated the structure–activity relationship between the needle length and cellular uptake behavior. They found that UCCSE entered tumor cells primarily via endocytosis, and that both intracellular accumulation and the associated tumor-cell killing effect increased markedly with longer needle-structures.
Experimental evaluations further showed that UCCSE achieved excellent antitumor efficacy at both the cellular and animal levels. In particular, the long-needle UCCSE exhibited prolonged blood circulation time and higher tumor accumulation, leading to the strongest tumor growth inhibition.
"Our finding provided an innovative morphology-engineering perspective for boosting the chemodynamic performance of single-atom nanozymes," said WANG Hui.
Schematic illustration of the synthesis of UCCSE and its tumor catalytic therapy. (Image by SHI Xinyi)
