2D Gadolinium Oxide Nanoplates as T₁ Magnetic Resonance Imaging Contrast Agents

Abstract

Millions of people a year receive magnetic resonance imaging (MRI) contrast agents for the diagnosis of conditions as diverse as fatty liver disease and cancer. Gadolinium chelates, which provide preferred T1 contrast, are the current standard but face an uncertain future due to increasing concerns about their nephrogenic toxicity as well as poor performance in high‐field MRI scanners. Gadolinium‐containing nanocrystals are interesting alternatives as they bypass the kidneys and can offer the possibility of both intracellular accumulation and active targeting. Nanocrystal contrast performance is notably limited, however, as their organic coatings block water from close interactions with surface Gadoliniums. Here, these steric barriers to water exchange are minimized through shape engineering of plate‐like nanocrystals that possess accessible Gadoliniums at their edges. Sulfonated surface polymers promote second‐sphere relaxation processes that contribute remarkable contrast even at the highest fields (r1 = 32.6 × 10−3 m Gd−1 s−1 at 9.4 T). These noncytotoxic materials release no detectable free Gadolinium even under mild acidic conditions. They preferentially accumulate in the liver of mice with a circulation half‐life 50% longer than commercial agents. These features allow these T1 MRI contrast agents to be applied for the first time to the ex vivo detection of nonalcoholic fatty liver disease in mice.

Magnetic Nanoparticles in Biology and Medicine: Past, Present, and Future Trends

“…However, concerns have been raised regarding potential toxicity, non-specific biodistribution, poor cellular uptake and retention, and the sub-optimal contrast enhancement of GCs [7,68,69]. As a result, many improvements and alternatives to GCs have been developed [7,[70][71][72][73][74][75][76][77].…”

Rational Design of a Gd(III)–Cu(II) Nanobooster for Chemodynamic Therapy Against Cancer Cells

“…On the contrary, the overexpression of GSH can reduce the reaction of Cu(II) to Cu(I) via Fenton-like reaction, further improving the production rate of •OH and reducing the antioxidant capacity of tumor cells ( Liu Y et al, 2019 ). From the abovementioned fact, the Gd(III)–Cu(II) complex showed better apoptosis-inducing effect than most copper compounds; this may be because the addition of Gd(III) increased the uptake of NPs by cancer cells, resulting in a more efficient CDT therapeutic effect ( Lee et al, 2015 ; Ren et al, 2019 ; Zeng et al, 2020 ; Stinnett et al, 2021 ).…”

Water‐dispersible Gadolinium Oxide Nanoplates as an Effective Positive Magnetic Resonance Imaging Contrast Agent

“…By a similar method, Stinnett et al. prepared Gd 2 O 3 nanoplates with the presence of cubic and monoclinic phase, however the contributions of monoclinic Gd 2 O 3 phase to the XRD pattern is minor [40] . In this study, our obtained XRD spectrum only displays the diffraction peaks characteristic for the cubic phase of Gd 2 O 3 without any other phase, indicating that the obtained Gd 2 O 3 nanoplates have high phase purity, or it also can be because the content of the monoclinic Gd 2 O 3 phase is too small to be detected by the XRD device.…”

“…Especially, the 2D Gd 2 O 3 nanoplates are much preferred for T 1 ‐weighted MRI as they are formed by assembly of single layer of unit cells, and thus have higher surface area than that of conventional spherical nanostructures with the same volume [36–39] . Furthermore, 2D nanostructures can provide a pathway for the close approach of water molecules through their unblocked edges because the surface ligands tend to bind to the larger faces of nanoplates, resulting in the T 1 relaxation was significantly enhanced [40–42] …”