(3eb) Engineering Nanosilver As Antibacterial, Biosensor and Bioimaging Material

This research involves the synthesis of nanostructured materials and the investigation of their properties targeting applications within the bio-medical field. Main focus of the research is to understand the fundamental principles and mechanisms of certain phenomena and to use this knowledge to design and synthesize nanostructured materials that possess the desired properties for their target application and at the same time overcome their shortcomings (e.g. toxicity or flocculation tendency). This would result in sustainable engineered nanomaterials in a rather “eco-friendly” way that offers its sought-out performance and minimizes risks (e.g. toxicity) to human health and environment [1]. Nanosilver particles are attractive for their use in bio-applications because of their plasmonic properties. For example, plasmonic Ag nanoparticles can be used in bio-imaging and/or in-vivo therapy (e.g. photothermal treatment of tumors). Even though silver has the lowest plasmonic properties in the UV-visible wavelength range, the more expensive gold is preferred for such bio-applications because of its lower toxicity. Nanosilver exhibits strong toxicity against biological systems because of its direct contact with the biological system and the released toxic Ag⁺ ions. However it was unclear whether the Ag⁺ ions or the direct contact with the particle surface plays the dominant role for this toxicity.

This motivated the initial target of the present research. By synthesizing nanocomposite Ag/SiO₂ nanoparticles, with closely controlled nanosilver size and content in the Ag/SiO₂ particles, it was possible to prevent nanosilver agglomeration or flocculation when dispersed in aqueous suspensions. This, in addition to the identification of the released Ag⁺ ion concentration by electrochemical measurements, led to decipher the role of the released Ag⁺ ions in nanosilver toxicity. It was discovered, for the first time, that when small (< 10 nm) nanosilver particles are employed, the Ag⁺ ion release is significant and thus Ag⁺ ions dominate the toxicity. In contrast, when nanosilver particles are rather large (>10 nm) the effect of Ag⁺ ions and the particles is comparable [2]. Furthermore, the origin of the released Ag⁺ ions was tracked to the leaching of the nanosilver surface layers [3]. 

The next step capitalized on this understanding. More specifically, synthesis of rather large nanosilver particles (> 30 nm) in order to avoid significant Ag⁺ ion release was performed. This time, however, these particles were hermetically-coated in-situ during their flame-synthesis by a nanothin silica film. The toxicity of these SiO₂-coated nanosilver particles was eliminated. This enabled creation of non-toxic plasmonic particles, ready to be employed as agents for bio-imaging. The nanothin SiO₂ shell also prevented nanosilver flocculation while it facilitated the bio-functionalization of such nanoparticles with a protein (bovine-serum-albumin). This was the first study to report the utilization of plasmonic nanosilver that is non-toxic as a potential biosensor [4].

When plasmonic nanoparticles are combined with another material, for example a magnetic component, multifunctional nanostructured materials are made. Such nanomaterials can combine more than one functionality, and thus, can be detected by multiple imaging techniques. Magnetic resonance imaging (MRI) is an example of a traditional technique, with which small magnetic particles can be used as contrast agents and for targeted drug delivery, by directing them to organs, tissues or tumors using an external magnetic field or for magnetically assisted cell sorting and separation. Furthermore, a SiO₂ coating on the surface of such magnetic nanoparticles facilitates their surface bio-functionalization and prevents their magnetic particle-particle interaction and flocculation or agglomeration. This coating prevents the release of toxic Ag⁺ ions and minimizes their toxicity, as it was tested against HeLa cells. In addition, their feasibility as superior biomarkers is explored by specifically binding them to live raji and HeLa cells and their detection was possible [5].

Further research involves the investigation of alternative materials suitable for bio-imaging and other bio- applications (e.g. nanophosphors [6]) and the nanotoxicological characterization of engineered nanomaterials [7].

[1] Sotiriou, G. A. & Pratsinis, S. E. Engineering nanosilver as antibacterial, biosensor and bioimaging material. Curr. Opin. Chem. Eng. in press, doi: 10.1016/j.coche.2011.1007.1001  (2010).

[2] Sotiriou, G. A. & Pratsinis, S. E. Antibacterial activity of nanosilver ions and particles. Environ. Sci. Technol. 44, 5649-5654 (2010).

[3] Sotiriou, G. A., Teleki, A., Camenzind, A., Krumeich, F., Meyer, A., Panke, S. & Pratsinis, S. E. Nanosilver on nanostructured silica: Antibacterial activity and Ag surface area. Chem. Eng. J. 170, 547-554 (2011).

[4] Sotiriou, G. A., Sannomiya, T., Teleki, A., Krumeich, F., Vörös, J. & Pratsinis, S. E. Non-Toxic Dry-Coated Nanosilver for Plasmonic Biosensors. Adv. Funct. Mater. 20, 4250-4257 (2010).

[5] Sotiriou, G. A., Hirt, A. M., Lozach, P. Y., Teleki, A., Krumeich, F. & Pratsinis, S. E. Hybrid, Silica-Coated, Janus-like Plasmonic-Magnetic Nanoparticles. Chem. Mater. 23, 1985-1992 (2011).

[6] Sotiriou, G. A., Schneider, M. & Pratsinis, S. E. Color-Tunable Nanophosphors by Codoping Flame-Made Y₂O₃ with Tb and Eu. J. Phys. Chem. C 115, 1084-1089 (2011).

[7] Sotiriou, G. A., Diaz, E., Long, M. S., Godleski, J., Brain, J., Pratsinis, S. E. & Demokritou, P. A novel platform for pulmonary and cardiovascular toxicological characterization of inhaled engineered nanomaterials. Nanotoxicology in press, doi:10.3109/17435390.2011.604439 (2011).