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Ultrasmall Nanoplatforms as Calcium‐Responsive Contrast Agents for Magnetic Resonance Imaging
Author(s) -
Moussaron Albert,
Vibhute Sandip,
Bianchi Andrea,
Gündüz Serhat,
Kotb Shady,
Sancey Lucie,
MottoRos Vincent,
Rizzitelli Silvia,
Crémillieux Yannick,
Lux Francois,
Logothetis Nikos K.,
Tillement Olivier,
Angelovski Goran
Publication year - 2015
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.201500312
Subject(s) - in vivo , magnetic resonance imaging , mri contrast agent , biophysics , calcium , gadolinium , nuclear magnetic resonance , in vitro , materials science , viability assay , biomedical engineering , chemistry , biochemistry , medicine , radiology , biology , physics , microbiology and biotechnology , metallurgy
The preparation of ultrasmall and rigid platforms (USRPs) that are covalently coupled to macrocycle‐based, calcium‐responsive/smart contrast agents (SCAs), and the initial in vitro and in vivo validation of the resulting nanosized probes (SCA‐USRPs) by means of magnetic resonance imaging (MRI) is reported. The synthetic procedure is robust, allowing preparation of the SCA‐USRPs on a multigram scale. The resulting platforms display the desired MRI activity—i.e., longitudinal relaxivity increases almost twice at 7 T magnetic field strength upon saturation with Ca 2+ . Cell viability is probed with the MTT assay using HEK‐293 cells, which show good tolerance for lower contrast agent concentrations over longer periods of time. On intravenous administration of SCA‐USRPs in living mice, MRI studies indicate their rapid accumulation in the renal pelvis and parenchyma. Importantly, the MRI signal increases in both kidney compartments when CaCl 2 is also administrated. Laser‐induced breakdown spectroscopy experiments confirm accumulation of SCA‐USRPs in the renal cortex. To the best of our knowledge, these are the first studies which demonstrate calcium‐sensitive MRI signal changes in vivo. Continuing contrast agent and MRI protocol optimizations should lead to wider application of these responsive probes and development of superior functional methods for monitoring calcium‐dependent physiological and pathological processes in a dynamic manner.