Novel (1S,3R)-RSL3-Encapsulated Polyunsaturated Fatty Acid Rich Liposomes Sensitise Multiple Myeloma Cells to Ferroptosis-Mediated Cell Death
Abstract
1. Background
2. Results
2.1. MM Cells Are Less Sensitive to the GPX4 Inhibitor, RSL3, than DLBCL Cells
2.2. MM Cells Generally Contain Higher Proportions of PL-MUFA than DLBCL Cell Lines
2.3. Exogenous PL-PUFA Induces Ferroptosis in MM Cells Proportional to the Degree of Acyl Chain Saturation
2.4. Exogenous PL-PUFA and RSL3 Synergise, Inducing Ferroptosis-Mediated Cell Death
2.5. Induction of Ferroptosis in MM Cells by PL-PUFA-Rich Liposomes
2.6. PL-PUFA-Rich Liposomes Containing RSL3 Induce Ferroptosis-Mediated Cell Death of MM Cells
3. Discussion
4. Methods
4.1. Drugs, Chemicals, and Other Reagents
4.2. Cell Culture
4.3. Assessment of Cell Viability
4.4. Assessment of Lipid ROS
4.5. Sample Preparation for Lipidomic Analyses
4.6. Live Cell Imaging
4.7. Western Blotting
4.8. Liposome Preparation
4.8.1. Micro-Fluidics Synthesis
4.8.2. Liposome Characterisation
4.8.3. Assessment of Liposome Uptake
4.8.4. Assessment of Liposome RSL3 Encapsulation
4.8.5. High-Performance Liquid Chromatography
4.9. Statistical Analyses
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
List of Abbreviations
DLBCL | Diffuse large B cell lymphoma |
FA | Fatty acid |
GPX4 | Glutathione peroxidase 4 |
HPLC | High-performance liquid chromatography |
LC-MS | Liquid chromatography–mass spectrometry |
LIP-1 | Liproxstatin-1 |
LOX | Lipooxygenase |
LPC | Lysophosphatidylcholine |
LPE | Lysophosphatidylethanolamine |
MM | Multiple myeloma |
MUFA | Monounsaturated fatty acid |
NEC-1 | Necrostatin-1 |
PC | Phosphatidylcholine |
PCD | Programmed cell death |
PDI | Polydispersity index |
PE | Phosphatidylethanolamine |
PI | Propidium iodide |
PL | Phospholipid |
PS | Phosphatidylserine |
PUFA | Polyunsaturated fatty acid |
RIPK | Receptor-interacting protein kinase |
ROS | Reactive oxygen species |
RSL3 | (1S,3R)-RSL3 |
SFA | Saturated fatty acid |
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Habib, A.; Mynott, R.L.; Best, O.G.; Revesz, I.A.; Prestidge, C.A.; Wallington-Gates, C.T. Novel (1S,3R)-RSL3-Encapsulated Polyunsaturated Fatty Acid Rich Liposomes Sensitise Multiple Myeloma Cells to Ferroptosis-Mediated Cell Death. Int. J. Mol. Sci. 2025, 26, 6579. https://doi.org/10.3390/ijms26146579
Habib A, Mynott RL, Best OG, Revesz IA, Prestidge CA, Wallington-Gates CT. Novel (1S,3R)-RSL3-Encapsulated Polyunsaturated Fatty Acid Rich Liposomes Sensitise Multiple Myeloma Cells to Ferroptosis-Mediated Cell Death. International Journal of Molecular Sciences. 2025; 26(14):6579. https://doi.org/10.3390/ijms26146579
Chicago/Turabian StyleHabib, Ali, Rachel L. Mynott, Oliver G. Best, Isabella A. Revesz, Clive A. Prestidge, and Craig T. Wallington-Gates. 2025. "Novel (1S,3R)-RSL3-Encapsulated Polyunsaturated Fatty Acid Rich Liposomes Sensitise Multiple Myeloma Cells to Ferroptosis-Mediated Cell Death" International Journal of Molecular Sciences 26, no. 14: 6579. https://doi.org/10.3390/ijms26146579
APA StyleHabib, A., Mynott, R. L., Best, O. G., Revesz, I. A., Prestidge, C. A., & Wallington-Gates, C. T. (2025). Novel (1S,3R)-RSL3-Encapsulated Polyunsaturated Fatty Acid Rich Liposomes Sensitise Multiple Myeloma Cells to Ferroptosis-Mediated Cell Death. International Journal of Molecular Sciences, 26(14), 6579. https://doi.org/10.3390/ijms26146579