Dysprosium(III)-Doped Nanotheranostic Agent for Ultra-High-Field MR Imaging-Guided Hepatocellular Carcinoma Therapy

Ultrahigh-field magnetic resonance imaging (UHF MRI) offers distinct advantages in medical imaging when compared to traditional low-field MRI technologies. However, due to inherent physical limitations, conventional contrast agents (such as gadolinium chelates and iron oxide nanoparticles) exhibit poor relaxation performance under strong magnetic field conditions. In contrast, the lanthanide element dysprosium (Dy) has demonstrated significant potential in constructing UHF MRI contrast agents, owing to its high magnetic moment and extremely short electron relaxation time. In this study, we developed a glutathione (GSH)-responsive self-immolative polymer theranostic platform (CA4@SIPD) chelated with Dy (III) for UHF MRI-guided hepatocellular carcinoma therapy. The polymer contains disulfide bonds that undergo GSH-triggered self-immolative cascade degradation in tumor sites, allowing controlled release of combretastatin A4 (CA4), a potent vascular-disrupting agent, to inhibit tumor growth. Simultaneously, the chelated Dy (III) endows the system with high-performance T 2 -weighted UHF MRI capabilities. This nanoplatform integrates UHF MRI compatibility with microenvironment-responsive drug delivery, providing real-time tumor-targeted visualization and synchronous therapeutic monitoring.