Metal-free and biocompatible TEMPO-containing nanoparticles for safe magnetic resonance imaging and stimuli-triggered drug release

Magnetic resonance imaging (MRI) is a cornerstone of modern diagnostic imaging. In clinical MRI diagnosis, MRI contrast agents are routinely employed to enhance the image contrast of specific areas in the body. However, conventional metal-based contrast agents pose potential toxicity risks, driving the development of safer metal-free alternatives. Nowadays, nitroxide radical contrast agents have emerged as a promising substitute, offering comparable efficiency without metallic components. In this study, we report three different nitroxide radical (TEMPO)-containing amphiphilic polymers that can self-assemble into spherical nanoparticles in aqueous solution. These nanoparticles exhibit increased longitudinal relaxivities (ranging from 0.58 to 0.88 mM −1  s −1 ), improved stability, and excellent biocompatibility. Following intravenous injection into mice, the nanoparticles produce significant MRI contrast enhancement in the urinary system for at least 1 h. Additionally, the synthesized polymers can function as effective carriers for anticancer drugs. Under reductive conditions, the drug-loaded nanoparticles undergo rapid release, achieving a final cumulative drug release of 62 %. Furthermore, the drug-loaded nanoparticles also show inhibitory effect on Hela cells. Overall, these TEMPO-containing polymer nanoparticles hold significant promise for applications in MRI and stimuli-triggered drug release.