A Metal-Free Nitroxide Radical Nanoliposome for MRI-Guided Therapy of Ulcerative Colitis

Ulcerative colitis (UC) remains challenging to diagnose and treat because of the limited sensitivity of current imaging techniques, the safety concerns associated with metal-based magnetic resonance imaging (MRI) contrast agents, and the insufficient efficacy of conventional anti-inflammatory therapies. Here, we report a metal-free theranostic nanoliposome (A@Clip) that integrates nitroxide radical-containing phospholipids (TEMPO-lipids) and 5-aminosalicylic acid (5-ASA) into a biocompatible liposomal platform for MRI-guided therapy of UC. The liposomal architecture enhances the T1 MRI performance of TEMPO radicals while enabling efficient reactive oxygen species scavenging and anti-inflammatory drug delivery. A@Clip exhibits excellent biocompatibility, promotes cellular uptake, and effectively suppresses oxidative stress and inflammatory responses in vitro. In a murine colitis model, A@Clip enables sensitive visualization of inflamed colon tissue and markedly alleviates disease progression, intestinal injury, inflammatory responses, and gut microbiota dysbiosis without detectable systemic toxicity. This work establishes a metal-free nanotheranostic strategy for integrating non-invasive MRI with anti-inflammatory therapy and provides a versatile platform for the precision management of inflammatory diseases.