Nanomaterials for Medical Imaging …
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stability, biodistribution, rapid clearance, low osmolality, and viscosity, and should
be biocompatible. The major problem associated with gadolinium contrast agents
(GCA) is the leakage of highly positive Gd
3+ ions compared to neutral or negative
charges. The ions of Gd
3+ competes with Ca
2+ , thereby altering the cellular functions
that require Ca
2+ [154]. Over three decades after the development of Gd-DTPA,
several chelates were developed to load Gd
3+ ions to avoid the leakage to prevent
toxicity [148, 155]. In preclinical MR imaging, Gd
3+ complexes were immediately
distributed in the bloodstream and cleared via kidneys and liver. The clearance time
of these complexes would vary from minutes to a few hours based on the functions of
a kidney that might cause nephrotoxicity called nephrogenic systemic fibrosis (NSF)
[156]. With emerging trends in nanotechnology and its advancements, incorporation
these Gd
3+ complexes into various nanostructures have been investigated. Let us
look some of the key examples of gadolinium-based nanostructures used for in vivo
imaging applications.
7.2 Liposomal Gd-Chelates Nanomaterials
Liposomes are types of drug carriers synthesized using phospholipids and are
promising drug delivery vehicles [158]. Liposomes can encapsulate hydrophilic,
hydrophobic drugs, and can be functionalized with the targeted antibody on the
surface [159]. Yang and his coworkers developed liposomes loaded with Magnevist
(Gd
3+ -DTPA) conjugated with interleukins-13 (IL-13) for the detection of glioma.
Glioma cells are overexpressed with IL-13 receptors alpha compared to normal brain
cells. Chelates of contrast agent loaded liposome conjugated with IL-13 antibodies
aid to cross the blood-brain barrier (BBB). The result of in vivo imaging shows that IL13-Liposomes-GD-DTPA possess enhanced contrast in the brain for early detection
of glioma [160]. Also, similar paramagnetic liposomes with single and dual integrin
functionalized liposomes loaded with Gd-DTPA were also potential candidates for
early diagnosis of cancer. Zhoug and his coworkers reported a lipopeptide coupled
with RGD peptide (as head) and palmitic acid. In vivo lung tumor model has been
developed at a volume of 50–100 mm
3 . Comparing non-targeted and targeted liposomes, targeted liposomes have long circulation in the blood and slowly accumulated
in tumor regions with an increase in MR intensity over time. Also, the localization
of targeted liposomes was high in the tumor than the normal tissues [161]. The same
group further developed dual-targeted liposomes, in vivo MR signal intensity was
higher than the Gd-DTPA, and RGD targeted contrast agents [162].
Imaging the inflammation in vivo for disease diagnosis, to understand the
pathology and targeting the immune system [163]. The inflammation region would
have an increased level of macrophages, wherein targeting these cells with mannose
enables them for better imaging. Tian et al. developed mannose coated gadolinium
nano-sized liposomes to determine the severity of acute pancreatitis inflammatory
conditions [164]. These liposomes are with a size range of 100 nm with an encapsulation efficiency of 85% Gd-DTPA. Two types of liposomes with and without
363
stability, biodistribution, rapid clearance, low osmolality, and viscosity, and should
be biocompatible. The major problem associated with gadolinium contrast agents
(GCA) is the leakage of highly positive Gd
3+ ions compared to neutral or negative
charges. The ions of Gd
3+ competes with Ca
2+ , thereby altering the cellular functions
that require Ca
2+ [154]. Over three decades after the development of Gd-DTPA,
several chelates were developed to load Gd
3+ ions to avoid the leakage to prevent
toxicity [148, 155]. In preclinical MR imaging, Gd
3+ complexes were immediately
distributed in the bloodstream and cleared via kidneys and liver. The clearance time
of these complexes would vary from minutes to a few hours based on the functions of
a kidney that might cause nephrotoxicity called nephrogenic systemic fibrosis (NSF)
[156]. With emerging trends in nanotechnology and its advancements, incorporation
these Gd
3+ complexes into various nanostructures have been investigated. Let us
look some of the key examples of gadolinium-based nanostructures used for in vivo
imaging applications.
7.2 Liposomal Gd-Chelates Nanomaterials
Liposomes are types of drug carriers synthesized using phospholipids and are
promising drug delivery vehicles [158]. Liposomes can encapsulate hydrophilic,
hydrophobic drugs, and can be functionalized with the targeted antibody on the
surface [159]. Yang and his coworkers developed liposomes loaded with Magnevist
(Gd
3+ -DTPA) conjugated with interleukins-13 (IL-13) for the detection of glioma.
Glioma cells are overexpressed with IL-13 receptors alpha compared to normal brain
cells. Chelates of contrast agent loaded liposome conjugated with IL-13 antibodies
aid to cross the blood-brain barrier (BBB). The result of in vivo imaging shows that IL13-Liposomes-GD-DTPA possess enhanced contrast in the brain for early detection
of glioma [160]. Also, similar paramagnetic liposomes with single and dual integrin
functionalized liposomes loaded with Gd-DTPA were also potential candidates for
early diagnosis of cancer. Zhoug and his coworkers reported a lipopeptide coupled
with RGD peptide (as head) and palmitic acid. In vivo lung tumor model has been
developed at a volume of 50–100 mm
3 . Comparing non-targeted and targeted liposomes, targeted liposomes have long circulation in the blood and slowly accumulated
in tumor regions with an increase in MR intensity over time. Also, the localization
of targeted liposomes was high in the tumor than the normal tissues [161]. The same
group further developed dual-targeted liposomes, in vivo MR signal intensity was
higher than the Gd-DTPA, and RGD targeted contrast agents [162].
Imaging the inflammation in vivo for disease diagnosis, to understand the
pathology and targeting the immune system [163]. The inflammation region would
have an increased level of macrophages, wherein targeting these cells with mannose
enables them for better imaging. Tian et al. developed mannose coated gadolinium
nano-sized liposomes to determine the severity of acute pancreatitis inflammatory
conditions [164]. These liposomes are with a size range of 100 nm with an encapsulation efficiency of 85% Gd-DTPA. Two types of liposomes with and without