Magnetic resonance imaging (MRI) has evolved into one of the most powerful, non-invasive diagnostic imaging techniques in medicine and biomedical research. The superior resolution and in-depth anatomical details provided by MRI are essential for early diagnosis of many diseases. Chemical contrast agents (CAs) have been widely used for improving the sensitivity and diagnostic confidence in MRI.
A new category of nanoconstructs for MRI contrast enhancement was created by loading gadolinium-based contrast agents (Gd-CAs) into the nanoporous structure of intravascularly injectable silicon particles (SiMPs). Microfabricated quasi-hemispherical (H-SiMPs) and discoidal (D-SiMPs) particles have been loaded with two different Gd-CAs, namely the clinically available Magnevist (MAG) and gadonanotubes (GNTs). For all four nanoconstructs, a boost in longitudinal proton relaxivity was observed. The relaxivity values are about 4 to 40 times larger than that of clinically available Gd-CAs (≈4 mM–ls–l per Gd3+ ion). The enhancement in MRI performance is attributed to the geometrical confinement of Gd-CAs into nanopores, which influences the paramagnetic behavior of the Gd3+ ions by altering both the inner- and outer-sphere contributions to the longitudinal relaxivity.
A boost in MRI was demonstrated upon geometrical confinement of two different GdCAs into the nanoporous structure of microfabricated particles. Geometrical confinement can reduce the ability of CAs to tumble, decrease the mobility of the water molecules, and favor clustering and mutual interactions among the loaded CAs, thus altering the original values of the governing parameters.
The nanoconstructs developed in this work constitute a formidable particle-based system for efficient intravascular delivery. The size, shape, and surface properties of the SiMPs can be rationally designed and tailored to enhance the accumulation of Gd-CAs within the biological target site, to alter overall half-life in blood, and to control degradation. The nanoconstructs developed could also play an important role in the development of single-cell imaging techniques, where high relaxivity and large localized Gd3+ concentration ([Gd3+] > 107/cell) are needed. Finally, these nanoconstructs could be loaded with multiple agents such as other nanoparticles, small molecules, and drugs to originate highly multifunctional systems with imaging and therapeutic capabilities.
This work was done by Paolo Decuzzi, Biana Godin-Vilentchouk, and Mauro Ferrari of the University of Texas Health Science Center at Houston; and Jeyarama Ananta and Lon Wilson of Rice University for Johnson Space Center. For further information, contact the JSC Technology Transfer Office at (281) 483-3809. MSC-24808-1