Abstract
The advancements of magnetic resonance imaging contrast agents (MRCAs) are continuously driven by the critical needs for early detection and diagnosis of diseases, especially for cancer, because MRCAs improve diagnostic accuracy significantly. Although hydrophilic gadolinium (III) (Gd3+) complex-based MRCAs have achieved great success in clinical practice, the Gd3+-complexes have several inherent drawbacks including Gd3+ leakage and short blood circulation time, resulting in the potential long-term toxicity and narrow imaging time window, respectively. Nanotechnology offers the possibility for the development of nontoxic MRCAs with an enhanced sensitivity and advanced functionalities, such as magnetic resonance imaging (MRI)-guided synergistic therapy. Herein, we provide an overview of recent successes in the development of renal clearable MRCAs, especially nanodots (NDs, also known as ultrasmall nanoparticles (NPs)) by unique advantages such as high relaxivity, long blood circulation time, good biosafety, and multiple functionalities. It is hoped that this review can provide relatively comprehensive information on the construction of novel MRCAs with promising clinical translation.
Highlights
Magnetic resonance imaging (MRI) is extensively used as a noninvasive, nonionizing, and radiation-free clinical diagnosis tool for detection and therapeutic response assessment of various diseases including cancer, because it can provide anatomical and functional information of regions-of-interest (ROI) with high spatial resolution through manipulating the resonance of magnetic nucleus (e.g., 1 H) in the body via an external radiofrequency pulse magnetic field [1,2,3,4,5,6,7]
There are two protocols for the synthesis of inorganic Gd3+ NDs: (1) direct synthesis of hydrophilic Gd NDs in water or polyol using a stabilizing agent which3+allows for crystal growth, Generally, there are two protocols for the synthesis of inorganic Gd NDs: (1) direct synthesis followed by ligand3+exchange with a more robust stabilizing agent to improve the colloidal stability of of hydrophilic Gd NDs in water or polyol using a stabilizing agent which allows for crystal growth, Gd3+ NDs in complex matrixes [62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81], and (2) preparation of hydrophobic Gd3+ NDs in high boiling followed by ligand exchange with a more robust stabilizing agent to improve the colloidal stability organic solvents by the pyrolysis methods, and subsequent transfer of the hydrophobic
With the help of nanotechnology, the recent research developments have progressed towards construction of renal clearable Magnetic resonance imaging contrast agents (MRCAs) with multifunctionality, which enables us to integrate several functions at the same time, such as simultaneous disease targeting, multimodal imaging, and therapy
Summary
Magnetic resonance imaging (MRI) is extensively used as a noninvasive, nonionizing, and radiation-free clinical diagnosis tool for detection and therapeutic response assessment of various diseases including cancer, because it can provide anatomical and functional information of regions-of-interest (ROI) with high spatial resolution through manipulating the resonance of magnetic nucleus (e.g., 1 H) in the body via an external radiofrequency pulse magnetic field [1,2,3,4,5,6,7]. The accuracy and reliability of disease diagnosis can be clearly improved by synergistically enhancing both T1 -/T2 -weighted contrast effects. Because of their unique physiochemical and magnetic properties, magnetic nanoparticles (MNPs) have attracted considerable attention in the construction of MRCAs with high performance during the last two decades (as shown in Figure 2), and they exhibit high potential for clinical applications in MRI-guided therapy. Molecules 2020, 25, x FOR PEER REVIEW (less than 10 nm) or biodegradable ability are able to balance the long blood circulation half-life time for imaging and efficient renal elimination. 2), and they exhibit high for clinical with ultrasmall size (typically less than properties, 10 nm in diameter) such as ultrasmall
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