Preparation, Characterization, Cytotoxicity, and Genotoxicity Evaluations of Thiolated- and S-Nitrosated Superparamagnetic Iron Oxide Nanoparticles: Implications for Cancer Treatment

Abstract

Iron oxide magnetic nanoparticles have been proposed for an increasing number of biomedical applications, such as drug delivery. To this end, toxicological studies of their potent effects in biological media must be better evaluated. The aim of this study was to synthesize, characterize, and examine the potential in vitro cytotoxicity and genotoxicity of thiolated (SH) and S-nitrosated (S-NO) iron oxide superparamagnetic nanoparticles toward healthy and cancer cell lines. Fe3O4 nanoparticles were synthesized by coprecipitation techniques and coated with small thiol-containing molecules, such as mercaptosuccinic acid (MSA) or meso-2,3-dimercaptosuccinic acid (DMSA). The physical-chemical, morphological, and magnetic properties of thiol-coating Fe3O4 nanoparticles were characterized by different techniques. The thiol groups on the surface of the nanoparticles were nitrosated, leading to the formation of S-nitroso-MSA- or S-nitroso-DMSA-Fe3O4 nanoparticles. The cytotoxicity and genotoxicity of thiolated and S-nitrosated nanoparticles were more deeply evaluated in healthy (3T3, human lymphocytes cells, and chinese hamster ovary cells) and cancer cell lines (MCF-7). The results demonstrated that thiol-coating iron oxide magnetic nanoparticles have few toxic effects in cells, whereas S-nitrosated-coated particles did cause toxic effects. Moreover, due to the superaramagnetic behavior of S-nitroso-Fe3O4 nanoparticles, those particles can be guided to the target site upon the application of an external magnetic field, leading to local toxic effects in the tumor cells. Taken together, the results suggest the promise of S-nitroso-magnetic nanoparticles in cancer treatment.

Superparamagnetic iron oxide nanoparticles dispersed in Pluronic F127 hydrogel: potential uses in topical applications

“…Superparamagnetic iron oxide nanoparticles, such as Fe 3 O 4 (magnetite), have been employed in a variety of biomedical applications, including diagnostics and drug delivery. [1][2][3][4][5][6][7][8][9][10] Due to the superparamagnetic behavior of Fe 3 O 4 at room temperature, these NPs have a large constant magnetic moment and act as a giant paramagnetic atom, quickly responding to applied magnetic elds without residual magnetism and coercivity. This behavior makes Fe 3 O 4 NPs attractive in a number of biomedical applications.…”

Nanotoxicology of Metal Oxide Nanoparticles

“…Most papers have described the in vitro and in vivo toxicity of chemically and/or physically synthesized iron oxide nanoparticles [32,87,90,91]. The toxicity of iron oxide nanoparticles can be attributed to the ROS induction of oxidative stress [92], and it is dependent on the particle surface, size distribution, zeta potential, and the chemical nature of the surface coating [32,87].…”

Nitric Oxide Releasing Nanomaterials for Cancer Treatment: Current Status and Perspectives

“…Seabra et al reported the synthesis, characterization, cytotoxicity, and genotoxicity of iron oxide (Fe 3 O 4 ) magnetic nanoparticles coated with mercaptosuccinic acid (MSA) and dimercaptosuccinic acid (DMSA) [77][78][79][80]. The thiol groups on the surface of Fe 3 O 4 nanoparticles were nitrosated, yielding S-nitrosated nanoparticles, which act as spontaneous NO donors.…”

“…The thiol groups on the surface of Fe 3 O 4 nanoparticles were nitrosated, yielding S-nitrosated nanoparticles, which act as spontaneous NO donors. Upon incubation with healthy cells (human lymphocytes, 3T3 fibroblasts) and human breast cancer cells (MCF-7), concentration-and time-dependent cytotoxicity and genotoxicity were observed [78][79][80]. As NO-releasing Fe 3 O 4 nanoparticles are superparamagnetic at room temperature [77], upon systemic application, these nanoparticles can be guided directly to the tumor cells (desired site of application) upon application of an external magnetic field.…”