Recent progress in the toxicity of nitric oxide-releasing nanomaterials

Nitric oxide (NO) is a signaling molecule controlling important biological processes. Depending on its concentration, location and cellular environment, NO can have protective or toxic effects. As NO is a free radical, several classes of NO donors/generators have been prepared and combined with nanomaterials, in particular, with polymeric nanoparticles. Engineered nanoparticles are attractive nanocarriers extensively used in biomedical applications, particularly, in cancer biology due to their ability to promote a site-target therapeutic effect, with minimum side effects to health tissues. NO-releasing nanoparticles can have direct toxic effects on tumor cells, or it can promote cancer cell sensitization for traditional cancer treatments. The combination of NO-releasing nanoparticles with conventional anticancer therapies is a promising approach in the reversion of multidrug resistance (MDR) cells. This review presents and discusses the recent progress in the cytotoxicity (tumoral and non-tumoral cell lines) of NO-releasing polymeric and/or polymer-coated nanomaterials and the in vivo biocompatibility of NO-releasing nanoparticles. Moreover, the ability of these nanoparticles to combat MDR, their mechanisms of toxicity and drawbacks are also discussed.