Investigating the Effect of Surface Chemistry of Mesoporous Silica Nanoparticles (MSNs) on MRI Performance

Magnetic resonance imaging (MRI) is a leading non-invasive medical imaging technique due to its well established spatially resolved images. To aid this diagnostic tool further, contrast agents have been designed to improve the quality of the images, with nanostructured MRI contrast agents showing exceptional promise in image enhancement at extremely low doses.¹ Relaxivity is the term used to assess the effectiveness of an MRI contrast agent on signal enhancement. Taking advantage of their generally high surface areas, nanostructured contrast agents often host large numbers of paramagnetic centres thereby increasing sensitivity through increased local concentration. Importantly, their bulky size improves relaxivity by contributing to slower rotational correlation time, resulting in longer <i>T₁ </i>relaxation times.² There is also increasing evidence that nanoscale design features, such as pore size and surface chemistry can influence water mobility and hence affect the ultimate capability of these nanostructures as MRI contrast agents.^2,3 Surface modifications can not only impact water diffusion, but also directly affect the local tumbling rate of a chelated paramagnetic centre.^4,5 However, understanding the structure-property relationship of designed nanostructured contrast agents is still relatively poor and therefore a more thorough investigation is required in order to improve their potency.<br/>The objective of this work is to explore how nearby surface modifications could influence the relaxation of Gd³⁺-chelates loaded in mesoporous silica nanoparticles (MSNs). We seek to gain a better grasp of how a gadolinium complex interacts with neighbouring functional groups, such as hydrophilic thiols or bulky phenyls, across a range of molar percentages present in the pores, to probe water diffusion and effects on local tumbling, and understand the resulting impact on relaxivity. As well as full structural characterisation, single-field and fast-field cycling relaxometry (SFR and FFC-NMRD, respectively) have been used to analyse the water diffusion/exchange behaviour within these composites. It was found that modifying the molar percentages of either functional group did not significantly affect the colloidal stability of the particles, nor their particle size, as determined by TEM. Functionalised particles displayed differing behaviour when analysed using SFR; the relaxivity of phenyl-functionalised MSNs did not exhibit a linear trend with an increasing number of phenyl groups present, indeed showing no influence from the bulky ligand, whereas the thiol-MSNs gave lower relaxivities as the thiol molar percentage increased. This is potentially due to the hydrophilic nature of the thiols and thus their interactions with water affecting the exchange rate. FFC-NMRD analysis revealed that both sets of functional groups influenced the paramagnetic Gd³⁺-chelate compared to non-functionalised MSNs. This work provides valuable insights into the importance of nanomaterial design features, in particular the location and nature of functional groups in MRI contrast agent design. An improved understanding of the interplay between these factors should prove useful in the development of such agents for diagnostics and sensing.<br/> <br/><b>References </b><br/>1. J. J. Davis, W.-Y. Huang and G.-L. Davies, <i>J. Mater. Chem.,</i> 2012, <b>22</b>, 22848-22850.<br/>2. G.-L. Davies, I. Kramberger and J. J. Davis, <i>Chem. Comm.</i>, 2013, <b>49</b>, 9704–9721.<br/>3. W.-Y. Huang, G.-L. Davies and J. J. Davis, <i>Chem. Comm.</i>, 2012, <b>49</b>, 60–62.<br/>4. F. Carniato, L. Tei, A. Arrais, L. Marchese and M. Botta, <i>Chem. Eur. J.</i>, 2013, <b>19</b>, 1421–1428.<br/>5. F. Carniato, L. Tei, M. Cossi, L. Marchese and M. Botta, <i>Chem. Eur. J.</i>, 2010, <b>16</b>, 10727–10734.