TY - JOUR
T1 - Ultrasmall Superparamagnetic Iron Oxide Nanoparticles as Nanocarriers for Magnetic Resonance Imaging
T2 - Development and in Vivo Characterization
AU - Si, Ge
AU - Hapuarachchige, Sudath
AU - Artemov, Dmitri
N1 - Publisher Copyright:
© 2022 American Chemical Society. All rights reserved.
PY - 2022/7/22
Y1 - 2022/7/22
N2 - Ultrasmall superparamagnetic iron oxide nanoparticles (uSPIOs) are attractive platforms for the development of smart contrast agents for magnetic resonance imaging (MRI). Oleic acid-capped uSPIOs are commercially available yet hydrophobic, hindering in vivo applications. A hydrophilic ligand with high affinity toward uSPIO surfaces can render uSPIOs water-soluble, biocompatible, and highly stable under physiological conditions. A small overall hydrodynamic diameter ensures optimal pharmacokinetics, tumor delivery profiles, and, of particular interest, enhanced T1MR contrasts. In this study, for the first time, we synthesized a ligand that not only fulfills the as-proposed properties but also provides multiple reactive groups for further modifications. The synthesis delivers a facile approach using commercially available reactants, with resultant uSPIO-ligand constructs assembled through a single-step ligand exchange process. Structural and molecular size analyses confirmed size uniformity and small hydrodynamic diameter of the constructs. On average, 43 reactive amine groups were present per uSPIO nanoparticle. Its r1relaxivity has been tested on a 7 Tesla MR instrument and is comparable to that of the clinically available T1gadolinium-based contrast agent GBCA (1 vs 3 mM-1s-1, respectively). A significant decrease in tumor T1(15%) within 1 h of injection and complete signal recovery after 2 h were detected with a dose of 7 μg Fe/g mouse. The agent also has high r2relaxivity and can be used for T2contrast-enhanced MRI. Taken together, good relaxation and delivery properties and the presence of multiple surface reactive groups can facilitate its application as a universal MRI-compatible nanocarrier platform.
AB - Ultrasmall superparamagnetic iron oxide nanoparticles (uSPIOs) are attractive platforms for the development of smart contrast agents for magnetic resonance imaging (MRI). Oleic acid-capped uSPIOs are commercially available yet hydrophobic, hindering in vivo applications. A hydrophilic ligand with high affinity toward uSPIO surfaces can render uSPIOs water-soluble, biocompatible, and highly stable under physiological conditions. A small overall hydrodynamic diameter ensures optimal pharmacokinetics, tumor delivery profiles, and, of particular interest, enhanced T1MR contrasts. In this study, for the first time, we synthesized a ligand that not only fulfills the as-proposed properties but also provides multiple reactive groups for further modifications. The synthesis delivers a facile approach using commercially available reactants, with resultant uSPIO-ligand constructs assembled through a single-step ligand exchange process. Structural and molecular size analyses confirmed size uniformity and small hydrodynamic diameter of the constructs. On average, 43 reactive amine groups were present per uSPIO nanoparticle. Its r1relaxivity has been tested on a 7 Tesla MR instrument and is comparable to that of the clinically available T1gadolinium-based contrast agent GBCA (1 vs 3 mM-1s-1, respectively). A significant decrease in tumor T1(15%) within 1 h of injection and complete signal recovery after 2 h were detected with a dose of 7 μg Fe/g mouse. The agent also has high r2relaxivity and can be used for T2contrast-enhanced MRI. Taken together, good relaxation and delivery properties and the presence of multiple surface reactive groups can facilitate its application as a universal MRI-compatible nanocarrier platform.
KW - MRI
KW - T-/ T-weighed imaging
KW - click chemistry
KW - contrast agent, preclinical cancer models
KW - ligand exchange
KW - uSPIO
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U2 - 10.1021/acsanm.2c01835
DO - 10.1021/acsanm.2c01835
M3 - Article
C2 - 37139481
AN - SCOPUS:85134823757
SN - 2574-0970
VL - 5
SP - 9625
EP - 9632
JO - ACS Applied Nano Materials
JF - ACS Applied Nano Materials
IS - 7
ER -