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Exceedingly Small Gadolinium Oxide Nanoparticles with Remarkable Relaxivities for Magnetic Resonance Imaging of Tumors
Author(s) -
Shen Zheyu,
Fan Wenpei,
Yang Zhen,
Liu Yijing,
Bregadze Vladimir I.,
Mandal Swadhin K.,
Yung Bryant C.,
Lin Lisen,
Liu Ting,
Tang Wei,
Shan Lingling,
Liu Yuan,
Zhu Shoujun,
Wang Sheng,
Yang Weijing,
Bryant L. Henry,
Nguyen Duong T.,
Wu Aiguo,
Chen Xiaoyuan
Publication year - 2019
Publication title -
small
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.785
H-Index - 236
eISSN - 1613-6829
pISSN - 1613-6810
DOI - 10.1002/smll.201903422
Subject(s) - magnetic resonance imaging , mri contrast agent , gadolinium , chelation , nuclear magnetic resonance , nanoparticle , dimer , biocompatibility , materials science , acrylic acid , chemistry , nanotechnology , monomer , polymer , medicine , radiology , physics , metallurgy
Gd chelates have occupied most of the market of magnetic resonance imaging (MRI) contrast agents for decades. However, there have been some problems (nephrotoxicity, non‐specificity, and low r 1 ) that limit their applications. Herein, a wet‐chemical method is proposed for facile synthesis of poly(acrylic acid) (PAA) stabilized exceedingly small gadolinium oxide nanoparticles (ES‐GON‐PAA) with an excellent water dispersibility and a size smaller than 2.0 nm, which is a powerful T 1 ‐weighted MRI contrast agent for diagnosis of diseases due to its remarkable relaxivities ( r 1 = 70.2 ± 1.8 mM −1 s −1 , and r 2 / r 1 = 1.02 ± 0.03, at 1.5 T). The r 1 is much higher and the r 2 / r 1 is lower than that of the commercial Gd chelates and reported gadolinium oxide nanoparticles (GONs). Further ES‐GON‐PAA is developed with conjugation of RGD2 (RGD dimer) (i.e., ES‐GON‐PAA@RGD2) for T 1 ‐weighted MRI of tumors that overexpress RGD receptors (i.e., integrin α v β 3 ). The maximum signal enhancement (ΔSNR) for T 1 ‐weighted MRI of tumors reaches up to 372 ± 56% at 2 h post‐injection of ES‐GON‐PAA@RGD2, which is much higher than commercial Gd‐chelates (<80%). Due to the high biocompatibility and high tumor accumulation, ES‐GON‐PAA@RGD2 with remarkable relaxivities is a promising and powerful T 1 ‐weighted MRI contrast agent.