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Biodegradable and Renal-Clearable Hollow Porous Iron Oxide Nanoboxes for In Vivo Imaging Ruixue Wei, Zhongyuan Cai, Bin W. Ren, Ao Li, Hongyu Lin, Ke Zhang, Hongming Chen, Hong Shan, Hua Ai, and Jinhao Gao Chem. Mater., Just Accepted Manuscript • DOI: 10.1021/acs.chemmater.8b03564 • Publication Date (Web): 01 Oct 2018 Downloaded from http://pubs.acs.org on October 1, 2018
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Chemistry of Materials
Biodegradable and Renal-Clearable Hollow Porous Iron Oxide Nanoboxes for In Vivo Imaging
Ruixue Wei,†,^ Zhongyuan Cai,‡,^ Bin W. Ren,† Ao Li,† Hongyu Lin,† Ke Zhang,§ Hongming Chen,† Hong Shan,§ Hua Ai,‡ and Jinhao Gao†,*
†
State Key Laboratory of Physical Chemistry of Solid Surfaces, The MOE Laboratory of
Spectrochemical Analysis & Instrumentation, The Key Laboratory for Chemical Biology of Fujian Province, and Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China. ‡
National Engineering Research Centre for Biomaterials, Sichuan University, Chengdu 610064, China.
§
Guangdong Provincial Engineering Research Center of Molecular Imaging, Center for Interventional
Medicine, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China.
^
Equal contribution
*
Address correspondence to
[email protected] 1
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ABSTRACT For in vivo imaging, it is important that imaging agents could be harmlessly eliminated from the body after performing their functions. Gadolinium-based magnetic resonance contrast agents have been suffering from low relaxivity, a potential risk of gadolinium deposition. The biocompatibility and biodegradability of γ-Fe2O3 nanoparticles render them promising as a potential candidate contrast agent for MRI applications. Herein, we develop a facile synthesis of biodegradable hollow porous iron oxide nanoboxes (HPIOs) with high r1 values and low r2/r1 ratios, allowing for superior contrast-enhanced T1 imaging. The zwitterionic dopamine sulfonate (ZDS) functionalized HPIOs (HPIOs@ZDS) could effectively avoid nonspecific protein adsorption and achieve controllable biodistribution. Furthermore, HPIOs@ZDS could be degraded into 4-5 nm fragments in the body and subsequently cleared by kidneys rapidly after magnetic resonance imaging, which significantly reduces potential long-term toxicity. These desirable features make HPIOs@ZDS a prominent T1 contrast agent for magnetic resonance angiography in vivo. These biodegradable and biocompatible HPIOs@ZDS holds great promise for highly sensitive and accurate detection of heart and vascular diseases in molecular imaging.
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Chemistry of Materials
INTRODUCTION Magnetic resonance imaging (MRI) is one of the most effective medical imaging techniques. In clinic, contrast agents (CAs) are often employed to increase the sensitivity of MRI and the accuracy of disease diagnosis.1-4 Over the past few decades, great efforts have been dedicated to design and synthesize high-performance contrast agents.5-10 According to their magnetic susceptibility, CAs are divided into T1 positive CAs (e.g., paramagnetic complexs of Mn2+ and Gd3+) and T2 negative CAs (e.g., superparamagnetic iron oxide nanoparticles, SPIOs).11-14 In practice, T1 contrast agents are preferred due to their bright signals in MRI images.15-17 However, Gd-based T1 contrast agents suffer from low relaxivity, short blood circulation time, and a potential risk for nephrogenic systemic fibrosis (NSF).18-19 Iron is an essential and abundant metal element in the human body. In terms of biocompatibility, iron-based materials is much more favored than Gd- or Mn-based materials.20-24 In the past decades, it has been shown that the magnetic moment of magnetite nanoparticles, a typical T2 contrast agent, is strongly suppressed due to surface spin-canting effect, when their size is reduced to
