Comprehensive and comparative studies on nanocytotoxicity of glyceryl monooleate- and phytantriol-based lipid liquid crystalline nanoparticles

Journal of Nanobiotechnology

Maciej Kozak¹  Zuzanna Pietralik-Molińska¹  Stefan Jurga²  Jakub Jagielski²  Łucja Przysiecka²  Dorota Flak²  Magdalena Diak²  Grzegorz Nowaczyk² 

[1] Department of Macromolecular Physics, Faculty of Physics, Adam Mickiewicz University, Uniwersytetu Poznańskiego 2, 61-614, Poznań, Poland;NanoBioMedical Centre, Adam Mickiewicz University, Wszechnicy Piastowskiej 3, 61-614, Poznań, Poland;

关键词: Cubosomes;    Cytotoxicity;    Genotoxicity;    Cytoskeleton integrity;    Reactive oxygen species generation;    Cellular internalization;   

DOI  :  10.1186/s12951-021-00913-5

来源: Springer

【 摘 要 】

BackgroundLipid liquid crystalline nanoparticles (LLCNPs) emerge as a suitable system for drug and contrast agent delivery. In this regard due to their unique properties, they offer a solubility of a variety of active pharmaceutics with different polarities increasing their stability and the possibility of controlled delivery. Nevertheless, the most crucial aspect underlying the application of LLCNPs for drug or contrast agent delivery is the unequivocal assessment of their biocompatibility, including cytotoxicity, genotoxicity, and related aspects. Although studies regarding the cytotoxicity of LLCNPs prepared from various lipids and surfactants were conducted, the actual mechanism and its impact on the cells (both cancer and normal) are not entirely comprehended. Therefore, in this study, LLCNPs colloidal formulations were prepared from two most popular structure-forming lipids, i.e., glyceryl monooleate (GMO) and phytantriol (PHT) with different lipid content of 2 and 20 w/w%, and the surfactant Pluronic F-127 using the top-down approach for further comparison of their properties. Prepared formulations were subjected to physicochemical characterization and followed with in-depth biological characterization, which included cyto- and genotoxicity towards cervical cancer cells (HeLa) and human fibroblast cells (MSU 1.1), the evaluation of cytoskeleton integrity, intracellular reactive oxygen species (ROS) generation upon treatment with prepared LLCNPs and finally the identification of internalization pathways.ResultsResults denote the higher cytotoxicity of PHT-based nanoparticles on both cell lines on monolayers as well as cellular spheroids, what is in accordance with evaluation of ROS activity level and cytoskeleton integrity. Detected level of ROS in cells upon the treatment with LLCNPs indicates their insignificant contribution to the cellular redox balance for most concentrations, however distinct for GMO- and PHT-based LLCNPs. The disintegration of cytoskeleton after administration of LLCNPs implies the relation between LLCNPs and F-actin filaments. Additionally, the expression of four genes involved in DNA damage and important metabolic processes was analyzed, indicating concentration–dependent differences between PHT- and GMO-based LLCNPs.ConclusionsOverall, GMO-based LLCNPs emerge as potentially more viable candidates for drug delivery systems as their impact on cells is not as deleterious as PHT-based as well as they were efficiently internalized by cell monolayers and 3D spheroids.Graphic Abstract

【 授权许可】

CC BY