Abstract: Gd-chelates based positive contrast agents have dominated the magnetic resonance imaging (MRI) contrast agent market for decades. Nevertheless, they have been reported to be nephrotoxic and the U.S. FDA has issued a general warning concerning their use. In this study, we synthesized exceedingly small magnetic iron oxide nanoparticles (ES-MIONs) for MRI of tumors, which is more biocompatible than Gd-chelates. We synthesized ES-MIONs with 7 different sizes below 5 nm, and found that 3.6 nm is the best particle size due to its highest r1 value (8.8 mM ^-1 s ^-1) and lowest r2/r1 ratio (2.6) (1.5 T). ^[1] To increase the r1 value and decrease the r2/r1 ratio, based on the ES-MIONs, we synthesized dotted core-shell nanoparticles with superhigh r1 value (70.0 mM ^-1 s ^-1) and very low r2/r1 ratio (1.98) (1.5 T) for high contrast T1-weighted MRI of tumors. MRI of tumors shows a superhigh tumor ΔSNR for the dotted core-shell nanoparticles (477 ± 44 %), which is much higher than that of Magnevist (75 ± 11 %). The highest tumor ΔSNR of our nanoparticles at low dosage of 0.5 mg / kg (84±9 %) is even higher than that of Magnevist at high dosage of 5.0 mg / kg (75±11 %), indicating a much lower nephrotoxicity risk for our nanoparticles. Based on the ES-MIONS, we further developed glutathione-responsive self-assembled magnetic gold nanowreath for MRI-guided photothermal therapy of tumors, and developed Fenton-reaction-acceleratable magnetic nanoparticles for MRI-guided high-efficiency ferroptosis therapy of orthotopic brain tumors.

Keywords: ES-MIONs, MRI contrast agents, tumor diagnosis, photothermal therapy, ferroptosis therapy

Biography: Dr. Zheyu Shen earned his PhD from Institute of Process Engineering, Chinese Academy of Sciences (Bei-jing) in July of 2008, under supervision of Prof. Guanghui Ma and Prof. Toshiaki Dobashi (Gunma University, Japan). After postdoctoral studies with Prof. Kazuhiro Kohama (Gunma University, Japan) and Prof. Sheng Dai (The University of Adelaide, Australia), he was appointed an associate professor (April, 2012) and promoted to full professor (December, 2015) at Ningbo Institute of Materials Technology & Engineering, Chinese Academy of Sciences. In July of 2016, he joined National Institutes of Health (USA) as a senior visiting scholar under supervision of Prof. Xiaoyuan Chen. Since August of 2019, he has been a full professor at Southern Medical University (Guang-zhou, China). His research interests include: MRI contrast agents, nanomaterials, biomaterials, cancer theranostics.