INVESTIGATING THE EFFECT OF METALLIC NANOPARTICLES (M-NPS) ON MODEL LIPID MEMBRANES

Precision translational oncology integrates basic and clinical research to transform fundamental discoveries into personalized and more effective cancer therapies. In this context, we investigate the efficacy of metal oxide nanoparticles in their ability to penetrate lipid bilayers and subsequently alter their structural integrity and lipid organization. These nanoparticles are functionalized with different molecular layers in order to tune their dispersivity in aqueous media and the interaction with cells. Moreover, our nanoparticles have shown promising antitumor properties in vivo, and ex vivo experiments. Thus, capturing how these nanoparticles interact with biological and model membranes is crucial for enhancing their performance and ensuring their success in clinical applications. Here, we investigate the fundamental interactions of metal oxide nanoparticles with artificial lipid membranes, namely Giant Unilamellar Vesicles (GUVs). These simplified model membranes are prepared using the electroformation or gel-assisted method and serve as an essential and effective representation of the plasma membrane's fundamental structure. It is important to note that biological membranes consist of a lipid bilayer, with each individual leaflet exhibiting a distinctive lipid composition. In healthy cells, the bilayer's asymmetry is crucial for retaining phosphatidylserine (PS) mainly within the inner leaflet, ensuring proper cellular function. However, in tumor cells, this balance is disrupted, leading to PS exposure on the outer leaflet. Therefore, in our in vitro studies, we examine the interactions between metal oxide nanoparticles and GUVs with different lipid compositions. First, we examine lipid bilayers with increasing amounts of cholesterol and explore how nanoparticles interact with them. Secondly, we evaluate different fractions of the negatively charged lipid PS in the GUVs. In our experiments, we thoroughly evaluate the leakage of a fluorescent, water-soluble dye encapsulated within the GUV contents, and we present a comparative analysis of the results under these different conditions. Our studies highlight the importance of elucidating the molecular mechanisms underlying these interactions. The authors disclose that the structure of the nanoparticles is patented. This work was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq 181274/2025-6, CNPq MAI/DAI 403663/2020-2, CNPq 304651/2021-4) and FAPESP (#2022/0446-4, #2025/01025-4).