Tumor microenvironment responsive T1-T2 dual-mode contrast agent Fe3O4@ZIF-8-Zn-Mn NPs for in vivo magnetic resonance imaging

Activated T-1-T-2 contrast agents can effectively improve the sensitivity and diagnosis accuracy of magnetic resonance imaging (MRI), but the construction of such contrast agents still remains a great challenge. In this work, a pH- and glutathione (GSH)-responsive T-1-T-2 dual-mode contrast agent, Fe3O4@ZIF-8-Zn-Mn nanoparticles (NPs), with simple components was constructed via simply assembly of paramagnetic Mn2+ ions (as T-1 contrast agent) and Fe3O4 NPs (as T-2 contrast agent) into a pH- and GSH-sensitive Zn-zeolitic imidazole framework (ZIF-8) matrix. Under neutral conditions, Fe3O4@ZIF-8-Zn-Mn NPs show good stability and weak T-1-T-2 dual-mode MRI contrast effect (r(1) = 0.82 mM(-1) s(-1), r(2) = 21.28 mM(-1) s(-1)) due to the magnetic interference between Fe3O4 NPs and paramagnetic Mn2+ ions. In contrast, under acidic environment (pH = 6.5-5.5) and in the present GSH (0-4 mM), Fe3O4@ZIF-8-Zn-Mn NPs can be disassembled and release Fe3O4 NPs and paramagnetic Mn2+ ions, which causes simultaneous recovery of T-1 and T-2 imaging performances with enhanced r(1) and r(2) relaxation values up to 6.9 and 9.9 times, respectively. Moreover, in vivo MRI experiments showed that after the intravenous injection of Fe3O4@ZIF-8-Zn-Mn NPs for about one hour, the T-1-weighted imaging of the tumor site becomes brighter with T-1 signal enhanced by about 31%, while the T-2-weighted imaging of the tumor site becomes darker with T-2 signal enhanced by nearly 30%, suggesting the great potential of Fe3O4@ZIF-8-Zn-Mn NPs to be used as a tumor microenvironment-responsive T-1-T-2 dual-mode contrast agent for sensitive tumor imaging.