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Updated: Jun 13, 2025
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Published on: April 28, 2014
Real-Time Single-Particle Tracking of Intracellular pH Dynamics during Ferroptosis Using Plasmonic Core-Satellite
Hua Liu1, Xiulin Fan2, Lin Wei3
1School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-Sen University, Shenzhen 518107, China.
Abstract:
Ferroptosis, an iron-dependent regulated cell death process, is characterized by lysosomal membrane permeabilization and pH dysregulation. Here, we report a DNA-programmed plasmonic nanoprobe based on i-motif-mediated gold core-satellite nanostructures (Au CSNSs) for single-particle resolution mapping of intracellular pH dynamics during ferroptosis. The i-motif DNA linker undergoes pH-dependent conformational switching, dynamically tuning the interparticle gap between 45 nm gold core nanoparticles (Au core NPs) and 15 nm gold satellite nanoparticles (Au satellite NPs). This architecture achieves a large localized surface plasmon resonance (LSPR) shift in the pH range of 5.6-6.8, enabling reversible and linear pH sensing (R2 = 0.97) with excellent photostability. During ferroptosis induced by exogenous iron, Au CSNSs displayed rapid spectral shifts corresponding to lysosomal H+ leakage, corroborated by acridine orange staining. Notably, mitophagy activation via rapamycin pretreatment sensitized cells to low-dose iron (1 μM), triggering earlier and more pronounced pH changes. This work establishes a novel platform for investigating pH-dependent signaling in ferroptosis, with implications for understanding mitochondria-lysosome crosstalk and developing targeted cancer therapies.
Insights
Researchers developed a novel DNA-programmed nanoprobe to map intracellular pH changes during ferroptosis, a cell death process. This tool reveals dynamic pH shifts, aiding the study of cell death mechanisms and cancer therapy development.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cell Biology
Background:
- Ferroptosis is an iron-dependent cell death marked by lysosomal changes and pH imbalance.
- Understanding intracellular pH dynamics is crucial for studying ferroptosis and developing therapies.
Purpose of the Study:
- To develop a novel nanoprobe for real-time, single-particle mapping of intracellular pH during ferroptosis.
- To investigate the role of pH dysregulation in ferroptosis and its modulation by mitophagy.
Main Methods:
- Fabrication of DNA-programmed gold core-satellite nanostructures (Au CSNSs) with i-motif linkers.
- Utilizing pH-dependent conformational changes of i-motif DNA to tune interparticle gaps and LSPR shifts.
- Monitoring intracellular pH dynamics in cells undergoing ferroptosis, with and without mitophagy induction.
Main Results:
- The Au CSNSs demonstrated reversible and linear pH sensing (R² = 0.97) in the relevant pH range (5.6-6.8).
- The nanoprobe successfully mapped rapid intracellular pH changes associated with lysosomal H+ leakage during iron-induced ferroptosis.
- Mitophagy activation accelerated and amplified ferroptosis-induced pH alterations.
Conclusions:
- A novel DNA-programmed nanoprobe platform enables precise monitoring of intracellular pH dynamics in ferroptosis.
- The findings highlight the critical role of pH dysregulation in ferroptosis and provide insights into mitochondria-lysosome crosstalk.
- This platform has potential applications in cancer therapy development and understanding cell death pathways.
