Biophysical insight into the interaction between  iron-based particles and liposomes

Biophysical insight into the interaction between  iron-based particles and liposomes


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Mgr. Jana Magdaléna Májeková100%100%100%
Mgr. Viktória Fedorová100%100%-

Biophysical insight into the interaction between  iron-based particles and liposomes

Dominik Michálek1 Zuzana Garaiová1 Martin Kopáni2 Daniel Kosnáč2 Tibor Hianik1
1Department of Nuclear Physics and Biophysics, Faculty of Mathematics, Physics and Informatics, Comenius University, Bratislava, Slovakia
2 Institute of Medical Physics, Biophysics, Informatics and Telemedicine, Faculty of Medicine, Comenius University, Bratislava, Slovakia

Iron is essential to most living organisms. Moreover, iron-based magnetic nanoparticles (Fe3O4 NPs) are synthetized and applied for their potential use in various biomedical fields due to their unique properties [1].  However, iron has been also found to accumulate and form larger aggregates in various organs, especially in the brain, which may be related to various, especially neuro-degenerative diseases [2]. Liposomes have gained an interest for their potential use as drug carriers [3] as well as biomimetic membrane models [4]. The interaction between Fe3O4 NPs and liposomes has not yet been investigated in sufficient details. We focused on the study of the interaction of two types of Fe3O4 NPs 1) less stable; zeta potential approx. -4 mV and 2) more stable; zeta potential approx. -38 mV. Three types of liposomes including a) positively charged 1,2-dioleoyl-3-trimethylammonium-propane chloride (DOTAP), b) negatively charged 1,2-dioleoylphosphatidylglycerol sodium salt (DOPG) and c) neutral phosphatidylcholine (PC) lipids were used. To note, DOTAP is used for nucleic acid/protein delivery [5], while PC and DOPG represent the main constituents of negatively charged biomembranes. Liposomes were prepared by hydration method in phosphate buffer solution followed by the extrusion through 100 nm filters. Samples were analyzed by means of size and zeta potential measurements using dynamic light scattering (DLS) and laser Doppler velocimetry methods using Zetasizer Nano ZS, respectively and visualized by the scanning electron microscopy (SEM). The hydrodynamic diameter and polydispersity index (PDI) obtained by DLS was approximately 150 nm (PDI 0,1) for pure liposomes, 2-3 µm (PDI 0,25) for less stable and 115 nm (PDI 0,15) for more stable Fe3O4 NPs. The strongest interaction, especially in the case of more stable and negatively charged Fe3O4 NPs was observed upon their incubation with DOTAP liposomes. This interaction was accompanied by the increase of hydrodynamic diameter of liposomes up to approx. 5 µm (PDI 0,7). The highest applied concentration of Fe3O4 NPs (100 µg/ml) moved the positive zeta potential value of DOTAP from 53 mV towards negative value -13 mV, which was followed by the formation of clusters as observed by the SEM. Altogether, the electrostatic nature of interaction between positively charged liposomes and negatively charged Fe3O4 NPs occurred. The formation of complexes with DOTAP liposomes can potentially improve the loading efficiency of Fe3O4 NPs into the cells. The further investigations are needed for the elucidation of their potential toxicity effects.


This work was funded under European Union’s Horizon 2020 research and innovation program through the Marie Skłodowska-Curie grant agreement No. 101007299 and by the Science Agency VEGA, project No. 1/0554/23.


[1] Tran, H. V. et al., Materials 15(2022), 503. [2] Maher B.A. et al. PNAS, 113 (2016), 10797-801. [3] Gao, W. et al., Liposome-like Nanostructures for Drug Delivery. J Mater Chem B. (2013), 1(48):10.1039. [4] Andrade, S. et al., Liposomes as biomembrane models: Biophysical techniques for drug-membrane interaction studies, Journal of Molecular Liquids, Volume 334, (2021), 116141. [5] Sun, M. et al., a Optimization of DOTAP/chol Cationic Lipid Nanoparticles for mRNA, pDNA, and Oligonucleotide Delivery. AAPS PharmSciTech 23, (2022).135.



Can you elaborate the difference between Fe3O4 NPs 1) less stable; zeta potential approx. -4 mV and 2) more stable; zeta potential approx. -38 mV and its role?


Hello, thank you for the question.

The zeta potential is an indicator of the stability of colloidal dispersions. Colloids with high zeta potential (negative or positive) are electrically stabilized, while colloids with low zeta potential (close to zero) are less or not stabilized. A higher negativity (or positivity) of the zeta potential of colloids causes their better resistance to aggregation in solution, on the other hand colloids with low zeta potential tend to aggregate. Fe3O4 NPs 1 (type A) were quasi-neutral, their zeta potential was very close to zero, therefore we consider them less stable, which was also manifested by their significant imediate aggregation in the buffer solution. Fe3O4 NPs 2 (type B) were negatively charged, their zeta potential was much more negative, therefore they were better dispersible and did not aggregate in the buffer solution. It was better to work with them because they had the same concentration throughout the solution all the time.