Developing a Gadolinium(III) Compound Based on Apoferritin for Targeted Magnetic Resonance Imaging and Dual-Modal Therapy of Cancer.

To integrate targeted diagnosis and treatment of cancer, we proposed to develop a gadolinium (Gd) agent based on the properties of apoferritin (AFt). To this end, we not only optimized a series of Gd(III) 8-hydroxyquinoline-2-carboxaldehyde-thiosemicarbazone compounds to obtain a Gd(III) compound (C4) with remarkable T 1 -weighted magnetic resonance imaging (MRI) performance and cytotoxicity to cancer cells in vitro but also constructed an AFt-C4 nanoparticle (NP) delivery system. Importantly, AFt-C4 NPs improved the targeting ability of C4 in vivo and showed enhanced MRI performance and tumor growth inhibition ratio relative to C4 alone. Furthermore, we confirmed that C4 and AFt-C4 NPs inhibited tumor growth through apoptosis, ferroptosis, and ferroptosis-induced immune response.