Lysine-based surfactants in nanovesicle formulations: the role of cationic charge position and hydrophobicity inin vitrocytotoxicity and intracellular delivery

Abstract

Understanding nanomaterial interactions within cells is of increasing importance for assessing their toxicity and cellular transport. Here, we developed nanovesicles containing bioactive cationic lysine-based amphiphiles, and assessed whether these cationic compounds increase the likelihood of intracellular delivery and modulate toxicity. We found different cytotoxic responses among the formulations, depending on surfactant, cell line and endpoint assayed. The induction of mitochondrial dysfunction, oxidative stress and apoptosis were the general mechanisms underlying cytotoxicity. Fluorescence microscopy analysis demonstrated that nanovesicles were internalized by HeLa cells, and evidenced that their ability to release endocytosed materials into cell cytoplasm depends on the structural parameters of amphiphiles.The cationic charge position and hydrophobicity of surfactants determine the nanovesicle interactions within the cell and, thus, the resulting toxicity and intracellular behavior after cell uptake of the nanomaterial. The insights into some toxicity mechanisms of these new nanomaterials contribute to reducing the uncertainty surrounding their potential health hazards.

Development of a biocompatible creatinine-based niosomal delivery system for enhanced oral bioavailability of clarithromycin

“…Some authors define them submicronic particles up to 200 nm (Nogueira et al, 2014). At this size, nano-materials might be easily taken up by cells and can potentially interact with biological systems, resulting in a wide range of applications, thus they are used widely as delivery systems for drug and gene (Robbens et al, 2010).…”

Photoprotection by Punica granatum seed oil nanoemulsion entrapping polyphenol-rich ethyl acetate fraction against UVB-induced DNA damage in human keratinocyte (HaCaT) cell line

“…The uptake of calcein, a membrane-impermeable fluorophore, and EAF-loaded NE into keratinocyte HaCat cells was observed through fluorescence microscopy. The control cells, treated with calcein alone, presented a punctate distribution, which is consistent with constitutive endocytosis of the external medium and indicates that the endosome membranes were not damaged [18,30]. When the calcein was co-incubated with EAFloaded NE a diffuse fluorescence into the cell cytoplasm was observed in some cells which suggest a low release of calcein from endosomal compartments.…”

“…HaCat cells were plated in 24-well plates at a density of 1×10 and their total fluorescence intensity was quantified, which corresponds to the cell internalization of nanoemulsion [18]. …”

Mechanisms Underlying Cytotoxicity Induced by Engineered Nanomaterials: A Review of In Vitro Studies

“…Interestingly, many of the research articles that consider the mechanisms underlying cytotoxicity, using specifically in vitro assays, have focused on more than one mechanism of cell interaction [ 20 , 31 ]. This is important in order to obtain some correlation between each cell disturbance effect and also to determine a sequence of mechanisms and specific NM–cell interactions that would ultimately to toxic effect.…”

“…Independently of the approach used to design a new drug delivery system, its toxicological properties must be assessed by using, for example, in vitro cellular models for a primary screening and also for the elucidation of some inherent mechanism underlying toxicity of each type of nanodevice. There is growing concern regarding the interrelationship between particle size, shape, chemical composition and toxicological effects of NMs, which are demonstrated by the increasing number of studies considering this subject [ 19 , 20 ].…”