New generation of nitric oxide-releasing porous materials: Assessment of their potential to regulate biological functions.

ABSTRACT

Nitric oxide (NO) presents innumerable biological roles, and its exogenous supplementation for therapeutic purposes has become a necessity. Some nanoporous materials proved to be potential vehicles for NO with high storage capacity. However, there is still a lack of information about their efficiency to release controlled NO and if they are biocompatible and biologically stable. In this work, we address this knowledge gap starting by evaluating the NO release and stability under biological conditions and their toxicity with primary keratinocyte cells. Titanosilicates (ETS-4 and ETS-10 types) and clay-based materials were the materials under study, which have shown in previous studies suitable NO gas adsorption/release rates. ETS-4 proved to be the most promising material, combining good biocompatibility at 180 µg/mL, stability and slower NO release. ETS-10 and ETAS-10 showed the best biocompatibility at the same concentration and, in the case of clay-based materials, CoOS is the least toxic of those tested and the one that releases the highest NO amount. The potentiality of these new NO donors to regulate biological functions was assessed next by controlling the mitochondrial respiration and the cell migration. NO-loaded ETS-4 regulates O2 consumption and cell migration in a dose-dependent manner. For cell migration, a biphasic effect was observed in a narrow range of ETS-4 concentration, with a stimulatory effect becoming inhibitory just by doubling ETS-4 concentration. For the other materials, no effective regulation was achieved, which highlights the relevance of the new assessment presented in this work for nanoporous NO carriers that will pave the way for further developments.