Polarizability Effects Dominate the Chromatographic Retention Behavior of Spheroidal and Elipsoidal Metallofullerene Nanospheres

The chromatographic retention behavior of spherical and elipsodial metallofullerenes provides a unique class for studying subtle intermolecular dispersive (London effect) and inductive (Debye effect) solution-state/solid-phase interactions. The known trimetallic nitride endohedral metallofullerene A₃N@C₈₀ isomers are nearly spherical A₃N@C₈₀-<i>I</i>_<i>h</i> and ellipsoidal A₃N@C₈₀-<i>D</i>_5<i>h</i>. These metallofullerene isomers are readily available with group IIIB and lanthanide trimetallic nitride clusters (A₃N)⁶⁺. In the current study, chromatographic HPLC retention behavior is monitored for two different HPLC stationary phases, pentabromobenzyl and pyrenylethyl and augmented by density functional theory computational results. Although dipole moments, lanthanide contraction, and charge transfer from the internal cluster (A₃N)⁶⁺ are important factors controlling chromatographic retention, our results suggest that the fullerene cage polarizability is the dominant factor controlling chromatographic separation of A₃N@C₈₀-<i>I</i>_<i>h</i> and elipsodial A₃N@C₈₀-<i>D</i>_5<i>h</i> isomers. Our study suggests that computational dipole moment and polarizability data allow accurate prediction of chromatographic retention behavior for fullerenes and metallofullerenes and can be extended to other π conjugated aromatic systems

Structure and proposed drug release mechanism of NsiL.

<p>a, in serum; b, in tumor cells.</p

Size distribution of different nanoparticles.

<p>PEGylated DSPC lipsome (black), SWNH(-CH₂-CH₂-COOH)_x (red), paclitaxel loaded SWNH(-CH₂-CH₂-COOH)_x (green), DSPC NsiL (blue), and DSPC NsiL without paclitaxel (light blue). Sizes are shown in diameters (mean ± S.D., n = 45).</p

Paclitaxel release profile of different carriers.

<p>a, in buffer paclitaxel release from PEGylated DOTAP liposome, SWNH(-CH₂-CH₂-COOH)_x and DOTAP NsiL; b, in serum paclitaxel release from PEGylated DOTAP liposome, SWNH(-CH₂-CH₂-COOH)_x and DOTAP NsiL; c, in serum paclitaxel release from PEGylated DSPC liposome at pH 4.6; d, in serum paclitaxel release from PEGylated DSPC liposome at pH 7.2 and 6.5. All liposomes were PEGylated. All SWNHs were functionalized. Numbers in the legends indicate the pH.</p

Cell binding affinity of different NPs.

<p>Different concentrations of particles were incubated with cell cultures, 40 µg/ml, 20 µg/ml, 10 µg/ml, 5 µg/ml, 2.5 µg/ml, 1.25 µg/ml, 0.625 µg/ml and blank control. A: NsiL with SK-BR-3; B: NsL with SK-BR-3; C: Herceptin NsiL with SK-BR-3; D: NsiL with BT-20; E: NsiL with BT-20; F: Herceptin NsiL with BT-20. NPs were labeled with rhB. Fluorescence emissions at 645 nm were measured.</p

Properties of lipid used in NsiL immunoliposome formulation.

<p>Properties of lipid used in NsiL immunoliposome formulation.</p

Study of NPs cytotoxicity by cell viability test.

<p>a, SK-BR-3 cells; b, BT-20 cells. Cells were treated with 640, 320, 160 and 80 µg/ml NPs (in lipid concentration). NsLDO and LipoDO are DOTAP NsL and PEGylated DOTAP liposomes, respectively. NsLDS and LipoDS are DSPC NsL and PEGylated DSPC liposomes, respectively. SWHN indicates SWNH(-CH₂-CH₂-COOH)_x.</p

Tb₂O@<i>C</i>₂(13333)‑C₇₄: A Non-Isolated Pentagon Endohedral Fullerene Containing a Nearly Linear Tb–O–Tb Unit

Terbium has been added to the list of elements that form oxide clusters inside fullerene cages. Tb2O@C2(13333)-C74 has been isolated as a byproduct of the electric arc synthesis of the azafullerene Tb2@C79N. Cocrystallization of Tb2O@C2(13333)-C74 with Ni(OEP) (where OEP is the dianion of octaethylporphyrin) in toluene yielded black needles of Tb2O@C2(13333)-C74·NiII(OEP)·1.5C7H8 that have been examined by single-crystal X-ray diffraction. The resulting structure shows that a nearly linear Tb–O–Tb unit is contained in a C2(13333)-C74, which has two sites where pentagons share an edge to form pentalene units at opposite ends of the fullerene. Unlike the usual situations where metal atoms in fullerenes that do not obey the isolated pentagon rule are situated within the folds of the pentalene units, the Tb atoms in Tb2O@C2(13333)-C74 are positioned to the side of the pentalene units and near-neighboring hexagons. The magnetic properties of Tb2O@C2(13333)-C74 have been examined starting from the experimental geometry, using ab-initio multiconfigurational methods. The computations predict that Tb2O@C2(13333)-C74 will show strong axiality, which would make it a single-molecule magnet with a large magnetic anisotropy barrier

Trimetallic Nitride Endohedral Fullerenes Carboxyl-Gd₃N@C₈₀: A New Theranostic Agent for Combating Oxidative Stress and Resolving Inflammation

Antioxidative and anti-inflammatory effects of trimetallic nitride endohedral fullerenes carboxyl-Gd₃N@C₈₀, a newly developed magnetic resonance imaging (MRI) contrast agent, were investigated. All hydrochalarone and carboxyl-functionalized fullerenes showed effective radical (hydroxyl and superoxide anion) scavenging, whereas the carboxyl-Gd₃N@C₈₀ more efficiently attenuated lipopolysaccharide (LPS) induced oxidative stress in macrophages. Carboxyl-Gd₃N@C₈₀ also suppressed LPS-elicited mRNA expression of pro-inflammatory inducible nitric oxide synthase and tumor necrosis factor-alpha, and upregulated antioxidative enzyme axis Nrf2 and heme oxygenase-1, possibly via ERK but not AKT signaling pathways. Therefore, carboxyl-Gd₃N@C₈₀ held a great promise in becoming a novel theranostic nanoplatform for simultaneously deliver MRI contrast and therapeutic functions to inflammation-related diseases

Detecting Chronic Post-Traumatic Osteomyelitis of Mouse Tibia via an IL-13Rα2 Targeted Metallofullerene Magnetic Resonance Imaging Probe

Differential diagnosis of chronic post-traumatic osteomyelitis (CPO) from aseptic inflammation remains challenging, since both pathological processes share similar clinical symptoms. Here we utilized a novel targeted metallofullerene nanoparticle based magnetic resonance imaging (MRI) probe IL-13-TAMRA-Gd₃N­@C₈₀­(OH)₃₀­(CH₂CH₂­COOH)₂₀ to detect CPO in mouse tibia via overexpressed IL-13Rα2 receptors. The functionalized metallofullerene was characterized by X-ray photoelectron spectroscopy. Upon lipopolysaccharide (LPS) stimulation, macrophage Raw 264.7 cells showed elevated IL-13Rα2 expression via immunofluorescence staining and increased MRI probe binding via built-in TAMRA fluorescence imaging. Trauma was induced in both tibia of mice and bacteria soaked suture was inserted into the right tibia to initiate infection. During the acute phase (1.5 weeks), luminol-bioluminescence imaging revealed much higher myeloperoxidase activity in the infected tibia compared to the sham. In the chronic phase (4 weeks), X-ray radiography illustrated bone deformation in the infected tibia compared to the sham. With <i>T</i>₁ weighted sequences, the probe clearly exhibited hyperintensity in the infection foci at both acute and chronic phases, which was not observed in the sham tibia. Histological analysis revealed severe bone structural destruction and massive inflammatory cell infiltration in the infected tibia. Immunohistochemistry confirmed abundant expression of IL-13Rα2 in the infection site. In summary, we developed a noninvasive imaging approach to detect and differentiate CPO from aseptic inflammation using a new IL-13Rα2 targeted metallofullerene MRI probe. In addition, for the first time, IL-13Rα2 was investigated as a unique biomarker in the context of osteomyelitis. Our data established a foundation for the translational application of this MRI probe in the clinical differentiation of CPO