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

ABSTRACT 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.