Colloids and Surfaces B: Biointerfaces 149 (2017) 243–249 Contents lists available at ScienceDirect Colloids and Surfaces B: Biointerfaces j o ur nal ho me pa ge: www.elsevier.com/locate/colsurfb Tuning the non-covalent confinement of Gd(III) complexes in silica nanoparticles for high T 1 -weighted MR imaging capability Svetlana V. Fedorenko a , Svetlana L. Grechkina b , Asiya R. Mustafina a , Kirill V. Kholin a , Alexey S. Stepanov a,b,∗ , Irek R. Nizameev a,c , Ildus E. Ismaev d , Marsil K. Kadirov a , Rustem R. Zairov a,b , Alfia N. Fattakhova b , Rustem R. Amirov b , Svetlana E. Soloveva a a A.E. Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Center of Russian Academy of Sciences, Arbuzov str., 8, 420088, Kazan, Russia b Kazan (Volga region) Federal university, Kremlyovskaya str., 18, 420008, Kazan, Russia c Kazan National Research Technological University, Kazan 420015, Russia d A.N. Tupolev Kazan National Research Technical University, 10, K. Marx St., Kazan, 420111, Russia a r t i c l e i n f o Article history: Received 29 June 2016 Received in revised form 6 September 2016 Accepted 13 October 2016 Available online 14 October 2016 Keywords: Positive contrast agents Silica nanoparticles MRI Gd(III) complexes Cytotoxicity Interfaces a b s t r a c t The present work introduces deliberate synthesis of Gd(III)-doped silica nanoparticles with high relaxivity at magnetic field strengths below 1.5 T. Modified microemulsion water-in-oil procedure was used in order to achieve superficial localization of Gd(III) complexes within 40–55 nm sized silica spheres. The relaxivities of the prepared nanoparticles were measured at 0.47, 1.41 and 1.5 T with the use of both NMR analyzer and whole body NMR scanner. Longitudinal relaxivities of the obtained silica nanoparticles reveal significant dependence on the confinement mode, changing from 4.1 to 49.6 mM −1 s −1 at 0.47 T when the localization of Gd(III) complexes changes from core to superficial zones of the silica spheres. The results highlight predominant contribution of the complexes located close to silica/water interface to the relaxivity of the nanoparticles. Low effect of blood proteins on the relaxivity in the aqueous colloids of the nanoparticles was exemplified by serum bovine albumin. T 1 - weighted MRI data indicate that the nanoparticles provide strong positive contrast at 1.5 T, which along with low cytotoxicity effect make a good basis for their application as contrast agents. © 2016 Elsevier B.V. All rights reserved. 1. Introduction Positive contrast agents (CAs) have gained great attention during recent decades due to their great impact in medicine [1–6]. Mononuclear Gd(III) complexes have got a wide applica- tion, although shortcomings of commercial CAs leave a room for improvement. Relaxivity enhancement due to slow tumbling of Gd(III) centres is a reason for increasing interest for nanopartic- ulate Gd(III)-based MRI CAs [5–12]. Silica coating of ultrasmall Gd(III) oxide or citrate nanoparticles, as well as mononuclear Gd(III) complexes is rather promising route to make nanopar- ticulate Gd(III)-based MRI contrast agents [13–18]. Silica coating provides hydrophilization of Gd 2 O 3 nanoparticles [13–15] or sil- ica nanoparticles serve as supports for surface immobilization by Gd(III) mononuclear complexes [16–21]. The extraction of Gd(III) ∗ Corresponding author at: A.E. Arbuzov Institute of Organic and Physical Chem- istry, Kazan Scientific Center of Russian Academy of Sciences, Arbuzov str., 8, Kazan, 420088, Russia. E-mail address: aleksestepanov@yandex.ru (A.S. Stepanov). ions by silica templates is one of possible immobilization ways [18], although a covalent silica surface functionalization by Gd(III) com- plexes is more widely represented in literature [16,17,19–21] for the immobilization. However, silica surface decoration by target peptides is required for selective binding with biotarget, which is exemplified by report [22] representing silica surface decoration by both gadolinium complexes and cell-penetrating peptides along with fluorophores. Nevertheless, simple noncovalent incorporation of mononuclear complexes into silica through a sol-gel method is worth noting for its advantage in remaining silica surface open for further decoration by biorelevant anchor groups [23–25]. The works of Caravan [26,27] highlight that subtle combination of rotation correlation times and water exchange rates is required for high r 1 and r 2 values at low fields (below 1.5 T). This tendency points to an impact of silica coating thickness in relaxivity of silica coated Gd(III) complexes. The importance of silica coating thickness in relaxivity is well documented for aqueous colloids of silica coated iron oxide nanoparticles [28,29]. Diffusion rate of water molecules through silica matrix to iron oxide cores is documented as main factor influencing relaxivity of the nanoparticles in aqueous col- http://dx.doi.org/10.1016/j.colsurfb.2016.10.025 0927-7765/© 2016 Elsevier B.V. All rights reserved.