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Abstract

Introduction Smart or responsive contrast agents (SCAs) can substantially improve specificity of magnetic resonance imaging (MRI) in studying processes on molecular and cellular level. These probes can alternate their MR signals upon change in the local environment, thus reporting occurrence of a particular physiological or pathological process. For instance, monitoring of concentration changes of ions or molecules that are involved in neuronal signaling can bring MR neuroimaging to the next level and allow investigation of brain activity in unprecedented fashion [1]. Methods We have developed a strategy to synthetically modify our SCAs that respond robustly to calcium and enable their combination with diverse functional molecules. Consequently, coupling of SCAs to dendrimers or nanoparticles or incorporation of SCA with the long hydrophobic chain into lypsomes results in preparation of various types of responsive nanosized probes. Results The dendrimeric SCA retains high longitudinal relaxivity (r1) change upon saturation with calcium while reducing the diffusion rate in vivo, which leads to the more constant contrast-enhanced signal in rat cerebral cortex (Figure 1). The SCAs covalently attached to the silica-based nanoparticles (NP-SCA) are also active towards calcium. After intravenous administration in mice, NP-SCA changes the MRI signal in both the renal pelvis and parenchyma upon the addition of CaCl2 solution. Finally, the liposome-based SCA indicates extremely large r1 changes at low magnetic field upon the relaxometric titration with calcium. Conclusions In vivo experiments performed with dendrimeric SCA showed very advantageous diffusion properties. More importantly, the nanoparticle-based SCAs demonstrated the capability of these responsive probes to report calcium concentration changes by means of MRI. Liposomic SCA indicates the possibility to strongly amplify MRI signal in calcium-dependent manner. A diversity in preparation procedures offers various possibilities to make very potent responsive agents. These nanoprobes hold great promise for use in molecular functional MRI.