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Updated: Jun 8, 2025
Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
Published on: March 15, 2024
In vivo imaging of ferroptosis through nanodynamic changes in lipid membranes
Ali Yasin Sonay1, Benedict Edward Mc Larney1, Elana Apfelbaum2
1Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center; New York, NY, USA.
Abstract:
Ferroptosis emerged as a cell death modality for drug resistant cancer cells, but there are currently no available biomarkers for imaging ferroptosis based therapies. To address this gab, we evaluated the nanodynamic changes in lipid membranes occurring during cell death to explore potential targeting opportunities to image cell death. We nano-sized gaps at late stages of ferroptosis can serve as entry points for dyes that can bind to cellular structures. These changes were accompanied with cellular signaling components similar to platelet activation, with phosphatidyl serine emerging on the surface of the cells and therefore as a potential target for imaging of programed cell death, including ferroptosis. Taking advantage of these changes in cell membrane dynamics, we employed a novel tumor-seeking dye CJ215 that can label apoptotic cells as recently described by us. We show that CJ215 accumulates in ferroptotic cells both in vitro and in vivo by binding to phosphatidyl serine, a process that is prevented by inhibition of ferroptosis. Since phosphatidyl serine exposure also occurs during apoptosis, CJ215 can serve to image both apoptosis and ferroptosis based therapy.
Insights
Researchers identified phosphatidylserine exposure during ferroptosis, a cell death pathway in drug-resistant cancers. A novel dye, CJ215, targets this exposure, enabling imaging of ferroptosis and apoptosis therapies.
Area of Science:
- Biochemistry
- Cell Biology
- Oncology
Background:
- Ferroptosis is a cell death pathway relevant to drug-resistant cancers.
- Currently, no biomarkers exist for imaging ferroptosis-targeted therapies.
- Understanding cell death mechanisms is crucial for developing effective cancer treatments.
Purpose of the Study:
- To investigate nanodynamic changes in lipid membranes during ferroptosis for potential imaging targets.
- To explore phosphatidylserine exposure as a biomarker for ferroptosis.
- To evaluate a novel dye, CJ215, for imaging ferroptosis and apoptosis.
Main Methods:
- Evaluation of nanodynamic changes in lipid membranes during ferroptosis.
- Analysis of cellular signaling components, including phosphatidylserine exposure.
- In vitro and in vivo testing of the tumor-seeking dye CJ215 for its accumulation in ferroptotic cells.
Main Results:
- Nanoscale gaps form in lipid membranes during late-stage ferroptosis, allowing dye entry.
- Phosphatidylserine exposure on the cell surface occurs during ferroptosis, similar to platelet activation.
- The dye CJ215 effectively accumulates in ferroptotic cells by binding to phosphatidylserine, both in vitro and in vivo.
- Inhibition of ferroptosis prevents CJ215 accumulation, confirming target specificity.
Conclusions:
- Phosphatidylserine exposure is a viable imaging target for ferroptosis.
- The novel dye CJ215 can image ferroptosis by targeting phosphatidylserine.
- CJ215 has the potential to image both apoptosis and ferroptosis, offering a versatile tool for cancer therapy monitoring.
