Manganese-impregnated mesoporous silica nanoparticles for signal enhancement in MRI cell labelling studies† R´ emy Guillet-Nicolas, abcd Myriam Laprise-Pelletier, bcd Mahesh M. Nair, ab Pascale Chevallier, d Jean Lagueux, d Yves Gossuin, e Sophie Laurent, f Freddy Kleitz * ab and Marc-Andr´ e Fortin * bcd Mesoporous silica nanoparticles (MSNs) are used in drug delivery and cell tracking applications. As Mn 2+ is already implemented as a “positive” cell contrast agent in preclinical imaging procedures (in the form of MnCl 2 for neurological studies), the introduction of Mn in the porous network of MSNs would allow labelling cells and tracking them using MRI. These particles are in general internalized in endosomes, an acidic environment with high saline concentration. In addition, the available MSN porosity could also serve as a carrier to deliver medical/therapeutic substances through the labelled cells. In the present study, manganese oxide was introduced in the porous network of MCM-48 silica nanoparticles (Mn–M48SNs). The particles exhibit a narrow size distribution (140 nm diam.) and high porosity (60% vol.), which was validated after insertion of Mn. The resulting Mn–M48SNs were characterized by TEM, N 2 physisorption, and XRD. Evidence was found with H 2 -TPR, and XPS characterization, that Mn(II) is the main oxidation state of the paramagnetic species after suspension in water, most probably in the form of Mn–OOH. The colloidal stability as a function of time was confirmed by DLS in water, acetate buffer and cell culture medium. In NMR data, no significant evidence of Mn 2+ leaching was found in Mn–M48SNs in acidic water (pH 6), up to 96 hours after suspension. High longitudinal relaxivity values of r 1 ¼ 8.4 mM 1 s 1 were measured at 60 MHz and 37  C, with the lowest relaxometric ratios (r 2 /r 1 ¼ 2) reported to date for a Mn–MSN system. Leukaemia cells (P388) were labelled with Mn–M48SNs and nanoparticle cell internalization was confirmed by TEM. Finally, MRI contrast enhancement provided by cell labelling with escalated incubation concentrations of Mn–M48SNs was quantified at 1 T. This study confirmed the possibility of efficiently confining Mn into M48SNs using incipient wetness, while maintaining an open porosity and relatively high pore volume. Because these Mn-labelled M48SNs express strong “positive” contrast media properties at low concentrations, they are potentially applicable for cell tracking and drug delivery methodologies. 1. Introduction In recent years, magnetic resonance imaging (MRI) has emerged as one of the most promising modalities enabling cell tracking in vivo. 1 Images of high anatomical resolution and excellent contrast in so tissues are possible with MRI, without using ionizing radiation. As such, MRI is an optimal choice for preclinical and clinical studies where the precise detection and biodistribution of injected cells over time are mandatory. 1 For this, the cells must be labelled with contrast agents (CAs) prior to injection, in order to allow their visualization. One of the most common CAs is iron-containing particles (SPIOs and USPIOS for example). They have been used for cell tracking in MRI since the beginning of the 1990s. 2–4 Because these superparamagnetic particles produce hypointense regions in MR images, i.e. strong signal attenuation due to T 2 shortening and T * 2 effects, they are designated as “negative” CAs. a D´ epartement de chimie, Universit´ e Laval, Qu´ ebec, QC G1V 0A6, Canada. E-mail: freddy.kleitz@chm.ulaval.ca; Fax: +1 418-656-7916; Tel: +1 418-656-7812 b Centre de recherche sur les mat´ eriaux avanc´ es (CERMA), Universit´ e Laval, Qu´ ebec, QC G1V 0A6, Canada c D´ epartement de g´ enie des mines, de la m´ etallurgie et des mat´ eriaux, Universit´ e Laval, Qu´ ebec, QC G1V 0A6, Canada d Axe M´ edecine R´ eg´ en´ eratrice, Centre de recherche du Centre hospitalier universitaire de Qu´ ebec (AMSVR-CRCHUQ), 10 rue de l'Espinay, Qu´ ebec, QC G1L 3L5, Canada. E-mail: marc-andre.fortin@gmn.ulaval.ca; Fax: +1 418-656-5343; Tel: +1 418-656- 8682 e Service de physique exp´ erimentale et biologique, Universit´ e de Mons, 20, Place du Parc, Mons, Belgium f Service de chimie g´ en´ erale, organique et biom´ edicale, Universit´ e de Mons, Mons, B7000, Belgium † Electronic supplementary information (ESI) available: TEM images, particle size distributions, XRD, TPR, magnetometric proles, T 1 and T 2 measurements at 60 MHz over time, NMRD proles of materials, P388 cell proliferation assay aer 4 h and T 1 -w. MR images of P388 cells incubated with a solution of M48SNs. See DOI: 10.1039/c3nr02969g Cite this: Nanoscale, 2013, 5, 11499 Received 8th June 2013 Accepted 3rd October 2013 DOI: 10.1039/c3nr02969g www.rsc.org/nanoscale This journal is ª The Royal Society of Chemistry 2013 Nanoscale, 2013, 5, 11499–11511 | 11499 Nanoscale PAPER Published on 07 October 2013. Downloaded by Memorial University of Newfoundland on 09/11/2013 14:25:19. 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