Gd@C₆₀[C(COOH)₂]₁₀ and Gd@C₆₀(OH)_x:  Nanoscale Aggregation Studies of Two Metallofullerene MRI Contrast Agents in Aqueous Solution

Abstract

Derivatized water-soluble Gd-based metallofullerenes are excellent MRI contrast agents with unusually large proton relaxivities for agents with no direct Gd−OH 2 bonding. In this study, dynamic light scattering (DLS), static light scattering (SLS), and transmission electron microscopy (TEM) have been used to characterize the propensity of two such species, Gd@C 60 [C(COOH) 2 ] 10 and Gd@C 60 (OH) x , to aggregate in aqueous solution, since aggregation is known to enhance proton relaxivities of MRI contrast agents by increasing their rotational correlation times (via more slowly tumbling aggregates). The present aggregation study has been conducted as a function of concentration, temperature, and pH and has revealed that both compounds aggregate at pH ) 9 to form spherical and irregular clusters having sizes between 30 and 90 nm, with little concentration or temperature dependency. Below pH ) 9, the aggregate sizes increase steadily and dramatically, reaching hydrodynamic diameters of 600−1000 nm by pH ) 5. Additionally, the intermolecular forces holding the aggregates together are weaker for Gd@C 60 [C(COOH) 2 ] than for Gd@C 60 (OH) x . We conclude that the tendency of these metallofullerene species to self-assemble into nanoscale aggregates in aqueous solution likely produces their unusually large, outer-sphere, pH-sensitive proton relaxivities.

A highly efficient and tumor vascular-targeting therapeutic technique with size-expansible gadofullerene nanocrystals

“…1b reveals that the gadofullerenes are spherical or ellipsoid particles with an average size of ca. 140 nm, which is larger than previously reported gadofullerenes derivatives [22,23]. Selected-area electron diffraction (SAED) of the sample shows clear Debye rings, suggesting that the GFNCs are indeed composed of multiple Gd@C 82 molecules in the core and with hydroxyl groups attached on the particle surface.…”

“…As motivated by a recent study on the synthesis of water soluble Gd@C 60 crystalline particles with a simple solid-liquid reaction [22], we prepared similar crystalline Gd@C 82 (OH) m nanoparticles using this novel technique. The purity of the sample was verified by both matrix-assisted laser desorption/ionization time-offlight mass spectrometry (MALDI-TOF MS) and high performance liquid chromatography (HPLC) measurements before using (Fig.…”

“…The crystalline gadofullerenes, e.g., Gd@C 60 [C(COOH) 2 ] 10 and Gd@C 60 (OH) x [22], (Gd@C 82 ) m (OH) n and others [25], have been found to own a common interesting physical property, namely, a size-expansible phase transition under heating. As illustrated in Figs 1c and d, we observed that the bulk Gd@C 82 polycrystals experience a conversable phase transition at ca.…”

Water-soluble fullerenes for medical applications

“…73 This might at first seem unexpected given that water molecules cannot directly interact with the gadolinium ion as it is shielded by the carbon cage, thus getting rid of all inner-sphere contributions to the relaxivity. Sitharaman et al 74 found that Gd@C 60 give a comprehensive outlook on the field. Zhang et al 82 synthesised two novel water-soluble Gd-EMFs also containing scandium, which again showed improved relaxivities compared to commercial agents.…”

High‐Relaxivity MRI Contrast Agents: Where Coordination Chemistry Meets Medical Imaging

“…[40][41][42] The peripheries of these cages are decorated with solubilizing groups to allow for application of C 60 in aqueous media. Relaxivities ranging from about 10 to as high as 38.5 mM -1 s -1 (30 MHz, 26 °C) are due entirely to second and outer-sphere relaxation, as there are no inner-sphere waters directly coordinated to the Gd.…”