Developed DNAzyme-based fluorescent sensors that specifically detect and image Fe2⁺ and Fe3⁺ ions in living cells, enabling the study of iron dynamics in biological processes and diseases like Alzheimer’s.
Background
Iron ions, specifically Fe2⁺ and Fe3⁺, are essential for numerous biological processes, including oxygen transport, DNA synthesis, and cellular energy production. Dysregulation of iron homeostasis is implicated in various neurodegenerative diseases, such as Alzheimer's disease, where altered iron redox states contribute to disease progression and oxidative stress. Understanding the spatial distribution and dynamic changes of these iron ions within living cells and tissues is crucial for understanding their roles in both normal physiology and pathological conditions. Advanced imaging techniques that can selectively and simultaneously monitor Fe²⁺ and Fe³⁺ ions are needed to gain deeper insights into iron-mediated biological processes and their impact on health and disease.
Current approaches to iron ion detection limits comprehensive biological studies. Traditional methods like mass spectrometry and magnetic resonance imaging (MRI) lack the ability to provide real-time, high-resolution spatial and temporal information about iron states within living systems. Fluorescent sensors available today often suffer from inadequate specificity, making it difficult to distinguish between Fe²⁺ and Fe³⁺ without cross-reactivity, leading to inaccurate measurements. Additionally, existing sensors are not optimized for use in complex biological environments, resulting in poor sensitivity and limited applicability in in vivo studies. These challenges highlight the need for more selective, sensitive, and versatile tools to accurately monitor iron redox states in biological contexts.
Technology description
The technology involves DNAzyme-based fluorescent sensors engineered to selectively detect and image Fe²⁺ and Fe³⁺ ions within living cells and tissues. These sensors leverage DNAzymes, which are DNA molecules with catalytic activity, specifically binding and cleaving substrates in the presence of iron ions. By attaching fluorophores and quenchers to the DNAzymes, a fluorescent signal is generated upon cleavage, allowing real-time visualization of iron ions. Designed for high selectivity, the sensors can simultaneously monitor both oxidation states of iron without cross-reactivity. This capability is essential for investigating iron redox cycling in biological processes and diseases such as Alzheimer’s, where altered Fe3⁺/Fe2⁺ ratios are associated with amyloid plaque regions. The sensors facilitate the exploration of iron distribution and dynamic changes in vivo, providing critical insights into the progression of neurodegenerative diseases and supporting the development of targeted therapeutic strategies.
What sets this technology apart is its exceptional ability to differentiate between Fe2⁺ and Fe3⁺ with high specificity and sensitivity, addressing the limitations of traditional iron measurement methods like mass spectrometry and MRI, which lack detailed spatial and temporal resolution. The DNAzyme sensors are developed through in vitro selection techniques tailored for each iron state, ensuring precise binding and catalytic activity. The catalytic beacon design enhances fluorescent signaling, making the sensors more reliable and applicable in live biological systems compared to existing fluorescent sensors. Their successful application in cellular models and brain tissues showcases their superior performance in monitoring iron dynamics in real-time. This advanced specificity and applicability provide a powerful tool for studying complex metal redox processes in biological systems, particularly in understanding and potentially mitigating diseases such as Alzheimer’s disease and ferroptosis.
Benefits
- High selectivity for Fe2⁺ and Fe3⁺ without cross-reactivity
- Simultaneous imaging of both iron oxidation states in living cells and tissues
- Enhanced sensitivity compared to existing sensors
- Provides detailed spatial and temporal information on iron dynamics
- Applicable in studying neurodegenerative diseases like Alzheimer's
- Aids in understanding iron redox cycling in biological processes
- Facilitates development of therapeutic strategies by visualizing iron distribution
Commercial applications
- Alzheimer’s disease diagnostics
- In vivo iron imaging
- Neurodegenerative research tools
- Drug development platforms
- Iron metabolism assays
Publication link
https://www.science.org/doi/epdf/10.1126/sciadv.ade7622
