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Dotted Core–Shell Nanoparticles for T 1 ‐Weighted MRI of Tumors
Author(s) -
Shen Zheyu,
Song Jibin,
Zhou Zijian,
Yung Bryant C.,
Aronova Maria A.,
Li Yan,
Dai Yunlu,
Fan Wenpei,
Liu Yijing,
Li Zihou,
Ruan Huimin,
Leapman Richard D.,
Lin Lisen,
Niu Gang,
Chen Xiaoyuan,
Wu Aiguo
Publication year - 2018
Publication title -
advanced materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 10.707
H-Index - 527
eISSN - 1521-4095
pISSN - 0935-9648
DOI - 10.1002/adma.201803163
Subject(s) - mri contrast agent , nephrotoxicity , magnetic resonance imaging , nanoparticle , materials science , confocal laser scanning microscopy , nuclear magnetic resonance , nuclear medicine , biomedical engineering , nanotechnology , medicine , kidney , radiology , physics
Gd‐based T 1 ‐weighted contrast agents have dominated the magnetic resonance imaging (MRI) contrast agent market for decades. Nevertheless, they are reported to be nephrotoxic and the U.S. Food and Drug Administration has issued a general warning concerning their use. In order to reduce the risk of nephrotoxicity, the MRI performance of the Gd‐based T 1 ‐weighted contrast agents needs to be improved to allow a much lower dosage. In this study, novel dotted core–shell nanoparticles (FeGd‐HN3‐RGD2) with superhigh r 1 value (70.0 mM −1 s −1 ) and very low r 2 / r 1 ratio (1.98) are developed for high‐contrast T 1 ‐weighted MRI of tumors. 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay and histological analyses show good biocompatibility of FeGd‐HN3‐RGD2. Laser scanning confocal microscopy images and flow cytometry demonstrate active targeting to integrin α v β 3 positive tumors. MRI of tumors shows high tumor ΔSNR for FeGd‐HN3‐RGD2 (477 ± 44%), which is about 6‐7‐fold higher than that of Magnevist (75 ± 11%). MRI and inductively coupled plasma results further confirm that the accumulation of FeGd‐HN3‐RGD2 in tumors is higher than liver and spleen due to the RGD2 targeting and small hydrodynamic particle size (8.5 nm), and FeGd‐HN3‐RGD2 is readily cleared from the body by renal excretion.