Yin Jinchang, Chen Deqi, Zhang Yu, Li Chaorui, Liu Lizhi, Shao Yuanzhi
School of Physics, State Key Laboratory of Optoelectronic Materials and Technologies, Sun Yat-sen University, Guangzhou 510275, P. R. China.
Phys Chem Chem Phys. 2018 Apr 18;20(15):10038-10047. doi: 10.1039/c8cp00611c.
Gadolinium oxide-based core-shelled nanoparticles have recently emerged as novel magnetic resonance imaging contrast agents for high relaxivity and tumor targeting. However, their relaxivity enhancement mechanism has not yet been clearly understood. We prepared highly dispersible and uniform core-shell structured nanoparticles by encapsulating silica spheres (90 nm in diameter) with gadolinium oxide shells of different thicknesses (from 1.5 nm to 20 nm), and proved experimentally that the shell thickness has an inverse effect on relaxivity. The core-shelled nanoparticles are of a larger relaxivity than the commercial contrast agent Gd-DTPA, with an enhancement from 1.8 to 7.3 times. Based on the Solomon-Bloembergen-Morgan theory which is usually adopted for interpreting the relaxation changes of water protons in Gd3+ chelates, we introduced a shielding ansatz of nanoshells and derived a concise formula specifically to correlate the relaxivity of this sort of core-shelled nanoparticles with the shell thickness directly. The formula calculation is well consistent with the experimental results, and the formula can be generally applied to evaluate the relaxation enhancement underlying the high relaxivity of any core-shelled nanoparticle. Furthermore, the core-shelled nanoparticles possess a negligible nanotoxicity according to the in vitro cytotoxicity and in vivo histopathology and hematology assays. The enhanced signals of in vivo tumor-targeted magnetic resonance imaging indicate that the ultrathin gadolinium oxide nanoshells may function as a potential candidate for advanced positive contrast agents in further clinical applications.
基于氧化钆的核壳纳米粒子最近作为具有高弛豫率和肿瘤靶向性的新型磁共振成像造影剂而出现。然而，它们的弛豫率增强机制尚未得到明确理解。我们通过用不同厚度（从1.5纳米到20纳米）的氧化钆壳包裹二氧化硅球（直径90纳米）制备了高度分散且均匀的核壳结构纳米粒子，并通过实验证明壳厚度对弛豫率有反比影响。核壳纳米粒子的弛豫率比商业造影剂钆喷酸葡胺大，增强了1.8至7.3倍。基于通常用于解释钆离子螯合物中水质子弛豫变化的所罗门 - 布洛姆伯根 - 摩根理论，我们引入了纳米壳的屏蔽假设，并推导出一个简洁的公式，专门将这种核壳纳米粒子的弛豫率与壳厚度直接关联起来。公式计算与实验结果非常一致，并且该公式可普遍应用于评估任何核壳纳米粒子高弛豫率背后的弛豫增强。此外，根据体外细胞毒性以及体内组织病理学和血液学分析，核壳纳米粒子具有可忽略不计的纳米毒性。体内肿瘤靶向磁共振成像的增强信号表明，超薄氧化钆纳米壳可能作为进一步临床应用中先进阳性造影剂的潜在候选物。
