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

Abstract

Understanding nanomaterial interactions within cells is of increasing importance for assessing their toxicity and cellular transport. Here, the authors developed nanovesicles containing bioactive cationic lysine-based amphiphiles and assessed whether these cationic compounds increase the likelihood of intracellular delivery and modulate toxicity. Different cytotoxic responses were found 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 internalised 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 behaviour after cell uptake of the nanomaterial. The insights into some toxicity mechanisms of these new nanomaterials contribute in reducing the uncertainty surrounding their potential health hazards.

Keywords::

• nanotoxicity
• pH-sensitivity
• drug delivery
• cell culture
• cell internalisation

Acknowledgements

This research was supported by Projects CTQ2009-14151- C02-02 and CTQ2009-14151-C02-01 of the Ministerio de Ciencia e Innovación (Spain), and MAT2012-38047-C02-01 of the Ministerio de Economía y Competitividad (Spain). The authors thank Dr Núria Cortadellas and Dr Jaume Comas for their expert technical assistance with the TEM and flow cytometry experiments, respectively. Daniele Rubert Nogueira holds a PhD grant from MAEC-AECID (Spain).