Tumor microenvironment responsive T 1 - T 2 dual-mode contrast agent Fe 3 O 4 @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, Fe 3 O 4 @ZIF-8-Zn-Mn nanoparticles (NPs), with simple components was constructed via simply assembly of paramagnetic Mn 2+ ions (as T 1 contrast agent) and Fe 3 O 4 NPs (as T 2 contrast agent) into a pH- and GSH-sensitive Zn-zeolitic imidazole framework (ZIF-8) matrix. Under neutral conditions, Fe 3 O 4 @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 Fe 3 O 4 NPs and paramagnetic Mn 2+ ions. In contrast, under acidic environment (pH = 6.5-5.5) and in the present GSH (0-4 mM), Fe 3 O 4 @ZIF-8-Zn-Mn NPs can be disassembled and release Fe 3 O 4 NPs and paramagnetic Mn 2+ 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 Fe 3 O 4 @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 Fe 3 O 4 @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.