Thermal- and pH-Dependent Size Variable Radical Nanoparticles and Its Water Proton Relaxivity for Metal-Free MRI Functional Contrast Agents

For development of the metal-free MRI contrast agents, we prepared the supra-molecular organic radical, <b>TEMPO-UBD</b>, carrying TEMPO radical, as well as the urea, alkyl group, and phenyl ring, which demonstrate self-assembly behaviors using noncovalent bonds in an aqueous solution. In addition, <b>TEMPO-UBD</b> has the tertiary amine and the oligoethylene glycol chains (OEGs) for the function of pH and thermal responsiveness. By dynamic light scattering and transmission electron microscopy imaging, the resulting self-assembly was seen to form the spherical nanoparticles 10–150 nm in size. On heating, interestingly, the nanoparticles showed a lower critical solution temperature (LCST) behavior having two-step variation. This double-LCST behavior is the first such example among the supra-molecules. To evaluate of the ability as MRI contrast agents, the values of proton (¹H) longitudinal relaxivity (<i>r</i>₁) were determined using MRI apparatus. In conditions below and above CAC at pH 7.0, the distinguishable <i>r</i>₁ values were estimated to be 0.17 and 0.21 mM^–1 s¹, indicating the suppression of fast tumbling motion of TEMPO moiety in a nanoparticle. Furthermore, <i>r</i>₁ values became larger in the order of pH 7.0 > 9.0 > 5.0. Those thermal and pH dependencies indicated the possibility of metal-fee MRI functional contrast agents in the future

Water-Proton Relaxivities of Radical Nanoparticles Self-Assembled via Hydration or Dehydration Processes

Nanoparticles capable of accumulating in tumor tissues are promising materials for tumor imaging and therapy. In this study, two radical nanoparticles (RNPs), denoted as <b>1</b> and <b>2</b>, composed of self-assembled ureabenzene derivatives possessing one or two amphiphilic side chains were demonstrated to be candidates for metal-free functional magnetic resonance imaging (MRI) contrast agents (CAs). Because of the self-assembly behavior of <b>1</b> and <b>2</b> in a saline solution, spherical RNPs of sizes ∼50–90 and ∼30–100 nm were detected. In a highly concentrated solution, <b>RNP 1</b> showed considerably small water-proton relaxivity values (<i>r</i>₁ and <i>r</i>₂), whereas <b>RNP 2</b> showed an <i>r</i>₁ value that was around 5 times larger than that of <b>RNP 1</b>. These distinct <i>r</i>₁ values might be caused by differences in the self-assembly behavior by a hydration or dehydration process. In vivo studies with <b>RNP 2</b> demonstrated a slightly enhanced <i>T</i>₁-weighted image in mice, suggesting that the RNPs can potentially be used as metal-free functional MRI CAs for <i>T</i>₁-weighted imaging