International Journal of Nanomedicine (Oct 2020)
Oxygen Functional Groups on MWCNT Surface as Critical Factor Boosting T2 Relaxation Rate of Water Protons: Towards Improved CNT-Based Contrast Agents
Abstract
Mateusz Michał Tomczyk,1 Sławomir Boncel,1 Artur Herman,2 Tomasz Krawczyk,1 Agata Jakóbik-Kolon,1 Mirosława Pawlyta,3 Maciej Krzywiecki,4 Artur Chrobak,5 Masafumi Minoshima,6 Fuminori Sugihara,7 Kazuya Kikuchi,6 Nikodem Kuźnik1 1Faculty of Chemistry, Silesian University of Technology, Gliwice, Poland; 2Department of Semiconductor Materials Engineering, Faculty of Fundamental Problems of Technology, Wroclaw University of Science and Technology, Wrocław, Poland; 3Faculty of Mechanical Engineering, Silesian University of Technology, Gliwice, Poland; 4Institute of Physics – Center for Science and Education, Silesian University of Technology, Gliwice, Poland; 5August Chełkowski Institute of Physics, University of Silesia, Katowice, Poland; 6Graduate School of Engineering, Osaka University, Osaka, Japan; 7Immunology Frontier Research Center, Osaka University, Osaka, JapanCorrespondence: Nikodem Kuźnik; Sławomir Boncel Email [email protected]; [email protected]: Salicyl (Sal) – among other oxygen functionalities – multi-walled carbon nanotubes (MWCNTs) and their nanohybrids are investigated as promising contrast agents (CA) in magnetic resonance imaging (MRI) or drug delivery platforms, due to their unique properties. The preliminary results and the literature reports were the motivation to endow high r2 relaxivities, excellent dispersibility in water, and biocompatibility to superparamagnetic MWCNTs nanohybrids. It was hypothesized that these goals could be achieved by, not described in the literature yet, two-stage oxygen functionalization of MWCNTs.Results: Two structurally different MWCNT materials differing in diameters (44 and 12 nm) and the iron content (4.7% and 0.5%) are studied toward the functionalization effect on the T2 relaxometric properties. MWCNT oxidation is typically the first step of functionalization resulting in “first generation” oxygen functional groups (OFGs) on the surface. Until now, the impact of OFGs on the relaxivity of MWCNT was not truly recognized, but this study sheds light on this issue. By follow-up functionalization of oxidized MWCNT with 4-azidosalicylic acid through [2+1] cycloaddition of the corresponding nitrene, “second generation” of oxygen functional groups is grafted onto the nanohybrid, ie, Sal functionality.Conclusion: The introduced OFGs are responsible for an almost 30% increase in the relaxivity, which leads to remarkable r2 relaxivity of 951 mM− 1s− 1 (419 (mg/mL)− 1s− 1), the unprecedented value reported to date for this class of CAs. Also, the resulting nanohybrids express low cytotoxicity and superb diffusion after subcutaneous injection to a mouse.Keywords: multi-walled carbon nanotubes, magnetic resonance imaging, MRI contrast agents, carbon nanotube functionalization, T2 relaxivity
