Metal-free nitroxide radical-based theranostic agent for MRI-guided therapy of ulcerative colitis

Abstract

Conventional metal-based contrast agents for magnetic resonance imaging (MRI) present concerns regarding potential chronic toxicity with prolonged use and inherently lack therapeutic functionality. Integrating the antioxidant 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO), which possesses intrinsic paramagnetic properties, into nanocarriers presents a promising solution to these challenges. Herein, we synthesized a TEMPO-grafted block copolymer that self-assembles into nanoparticles encapsulating olsalazine (OS) to create TBATM@OS. In vitro experiments demonstrated the potential of TBATM@OS for MRI-guided drug delivery and effective clearance of reactive oxygen species (ROS). Consequently, TBATM@OS enables clear MRI detection of intestinal inflammation and effectively reduces inflammation, unlike the clinical agent Magnevist, which was unable to visualize inflamed sites. Mechanistic studies revealed that TBATM@OS modulates TNF signaling pathways, restores intestinal barrier homeostasis, and balances gut microbiota. This bifunctional nanoagent provides a therapeutic strategy for imaging and sustained alleviation of colon inflammation.