Anti-oxidative effects and harmlessness of asymmetric Au@Fe3O4 Janus particles on human blood cells

Abstract

The physical properties of asymmetric Janus particles are highly promising for future biomedical applications. However, only a few data is available on their biological impact on human cells. We investigated the biological impact of different Au@Fe3O4 Janus particle formulations in vitro to analyse specific uptake modalities and their potential cytotoxic effects on human cells of the blood regarding intravenous injection. We demonstrate that Au@Fe3O4 Janus particles exhibit a similar or even better biocompatibility compared to the well-studied spherical iron oxide nanoparticles. The impact of Janus particles on cells depends mainly on three factors. (1) Surface functionalization: NH2-functionalization of the Au or iron oxide domain induces a pronounced reduction of cell viability in contrast to non-functionalized variants which is caused by the damage of intracellular membranes. (2) The nature of the metal oxide component, greatly affects cell viability, as shown by a comparison with Au@MnO Janus particles. (3) The overall surface charge and the size of nanoparticles have a higher impact on internalization and cellular metabolism than the Janus character per se. Interestingly, Janus particle associated DNA damage is independent of the effects on the cellular ATP level. However, not only the structure and functionalization of the Janus particle surface determines the particle's adhesion and intracellular fate, but also the constitution of the cell surface as shown by different modification experiments. The multifactorial in vitro approach presented in this study demonstrated the high capability of the Janus particles. Especially Au@Fe3O4 Janus particles bear great potential for applications in vivo.

A plasma protein corona enhances the biocompatibility of Au@Fe3O4 Janus particles

“…A high level of reactive oxygen species was also shown for spherical Fe 3 O 4 -SiO 2 -PEG in previous studies[15]. Interestingly, it was shown in literature that the gold domain of Au-thiol@Fe 3 O 4 -SiO 2 -PEG JPs exhibited an anti-oxidative potential against generated reactive oxygen species, thereby improving the biocompatibility of the JPs[15]. This may be especially important due to the higher cellular uptake of corona coated JPs compared to pristine JPs and control particles, which is in agreement with previous results showing an increased nanoparticle attachment and uptake into endothelial cells after corona formation[30].The in vivo biodistribution of nanoparticles critically impacts potential biomedical applications.…”

“…As the protein corona constitutes the "bio/nano interface", which affects the biological identity of the nanoparticles by determining their biocompatibility and transport [29,30] the Janus structure prevented agglomeration of Au-thiol@Fe 3 O 4 -SiO 2 -PEG-NH 2 particles, thereby stabilizing the particle in solution. A tendency to agglomeration caused by surface NH 2 -groups has been described previously [15,67], showing an increase of hydrodynamic diameters of amine-modified polystyrene nanoparticles as compared to control nanoparticles [67]. As only the Fe 3 O 4 -SiO 2 -PEG-NH 2 particles showed a zeta potential > +20 mV in water, we hypothesize that particle aggregation is favored by charge effects.…”

“…The formation of reactive oxygen species caused by different nanoparticles resulted in apoptotic processes was established[71,72]. A high level of reactive oxygen species was also shown for spherical Fe 3 O 4 -SiO 2 -PEG in previous studies[15]. Interestingly, it was shown in literature that the gold domain of Au-thiol@Fe 3 O 4 -SiO 2 -PEG JPs exhibited an anti-oxidative potential against generated reactive oxygen species, thereby improving the biocompatibility of the JPs[15].…”

“…Even though nanoparticle protein coronas have been intensively investigated for liposomes or symmetric and isotropic polystyrene, magnetite, and silica nanoparticles [30,[35][36][37], it is yet unclear whether asymmetric and amphiphilic Au@Fe 3 O 4 nanoparticles exhibit similar features regarding the formation of a protein corona similar to spherical nanoparticles [30,[38][39][40]. In view of the widespread biomedical applications of JPs, they have a similar biodistribution [15] as their spherical and isotropic component constituent blocks.…”

“…The Au@Fe 3 O 4 and spherical Fe 3 O 4 nanoparticles were synthesized as described previously with thiol groups at the gold domain and a silica-PEG shell at the iron oxide domain (Authiol@Fe 3 O 4 -SiO 2 -PEG and Fe 3 O 4 -SiO 2 -PEG) [15,16]. Gold nanoparticles were prepared by a M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT 6 modified procedure [42] followed by the synthesis of Au@Fe 3 O 4 heteroparticles using a seedmediated chemical protocol [43,44].…”