Preparation and In Vitro Evaluation of a MRI Contrast Agent Based on Aptamer-Modified Gadolinium-Loaded Liposomes for Tumor Targeting.

The aim of this study was to prepare aptamer-modified liposomes loaded with gadolinium (Gd) to enhance the effective diagnosis for tumor by MRI. A modified GBI-10 (GBI-10m) was used to prepare targeted liposomes (GmLs). Liposomes with GBI-10 aptamer (GLs) and without aptamer (non-targeted liposomes (NLs)) were also prepared as controls. The particle size and zeta potential of GmLs, GLs, and NLs were all assayed. A clinical 3.0 T MR scanner was employed to assess the imaging efficiency and measure the longitudinal relaxivity (r 1) of the above liposomes. Confocal laser scanning microscopy and flow cytometry were used to analyze and compare the targeting effects of GmLs, GLs, and NLs to MDA-MB-435s cells at 37°C. The particle size of the prepared liposomes was scattered at 100-200 nm, and their values of r 1 were ∼4 mM-1 s-1. The images of confocal laser scanning microscopy showed that GmLs in the cytoplasm were significantly more than GLs and both GmLs and GLs were more than NLs. The fluorescence intensity of GmLs was increased by about two times than that of GLs and three times than that of NLs by flow cytometry. Therefore, the GmLs in this initial study were suggested to be a potential MRI contrast agent at 37°C for diagnosing tumors with the protein of tenascin-C over-expressed.

Association between promoter polymorphisms of interleukin-4 gene and allergic rhinitis risk: a meta-analysis.

The relationship of interleukin-4 (IL-4) C-33T and C-590T (C-589T) gene polymorphisms with allergic rhinitis was analyzed. Data about the case control studies of IL-4 gene promoter polymorphisms [C-33T and C-590T (C-589T)] and their association with allergic diseases and correlation between serum IL-4 levels and allergic rhinitis were retrieved. The Stata 12.0 statistical software was applied to analyze the correlation between IL-4 gene polymorphisms and allergic rhinitis. The meta-analysis result of TT/CC genotype of -590 (-589) polymorphism showed a significant association with allergic diseases [OR=1.93, 95% CI (1.61-2.31), P=0.00]. Meta-analysis of the TT+TC versus CC genotype of IL-4 C-33/T polymorphism revealed significant associations with allergic diseases [OR=3.23, 95% CI (1.13-9.25), P=0.03]. Meanwhile, there was a significant correlation between serum IL-4 levels and allergic rhinitis [OR=2.52, 95% CI=(1.80-3.23), P=0.00]. IL-4 gene -590 TT genotype may increase the risk of allergic rhinitis and the T allele mutation of -33 might be correlated with allergic rhinitis.

Artificial superconducting Kondo lattice in a van der Waals heterostructure.

Engineering Kondo lattice with tailored functionality is desirable for elucidating the heavy fermion physics. We realize the construction of an artificial Kondo lattice/superconductor heterojunction by growing monolayer VSe2 on bulk 2H-NbSe2 with molecular beam epitaxy. Spectroscopic imaging scanning tunneling microscopy measurements show the emergence of a new charge density wave (CDW) phase with 3 × 3 periodicity on the monolayer VSe2. Unexpectedly, a pronounced Kondo resonance appears around the Fermi level, and distributes uniformly over the entire film, evidencing the formation of Kondo lattice. Density functional theory calculations suggest the existence of magnetic interstitial V atoms in VSe2/NbSe2, which play a key role in forming the CDW phase along with the Kondo lattice observed in VSe2. The Kondo origin is verified from both the magnetic field and temperature dependences of the resonance peak, yielding a Kondo temperature of ~ 44 K. Moreover, a superconducting proximity gap opens on monolayer VSe2, whose shape deviates from the function of one-band BCS superconductor, but is reproduced by model calculations with heavy electrons participating the pairing condensate. Our work lays the experimental foundation for studying interactions between the heavy fermion liquids and the superconducting condensate.

Significance of Diffusion Tensor Imaging of Vastus Medialis Oblique in Recurrent Patellar Dislocation.

BACKGROUND: Numerous studies have investigated the influence of osseous factors on patellofemoral joint instability, but research on the influence of dynamic muscle factors in vivo is still in the exploratory stage. This study aimed to use magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) to evaluate vastus medialis oblique (VMO) fiber bundles in patients with recurrent patellar dislocation to explore the changes in muscle morphology and function. METHODS: This prospective study involved 30 patients (7 males and 23 females; average age, 21.4 ± 3.8 years) clinically diagnosed with recurrent patellar dislocation in Peking University Third Hospital and 30 healthy volunteers matched for age, sex, and body mass index in our medical school between January 2014 and October 2014. None of the patients had a recent history of traumatic patellar dislocation or transient patellar dislocation. All patients underwent conventional MRI and DTI of the knee. The cross-sectional area of the VMO on MRI and the fractional anisotropy (FA), apparent diffusion coefficient (ADC), and primary (λ1), secondary (λ2), and three-level characteristic (λ3) values on DTI were measured. The independent-samples t-test was used to compare these parameters between the two groups. RESULTS: Compared with the control group, the patient group showed significantly higher FA values (0.39 ± 0.05 vs. 0.33 ± 0.03) and significantly lower ADC (1.51 ± 0.13 vs. 1.58 ± 0.07), λ2 (4.96 ± 0.13 vs. 5.04 ± 0.07), and λ3 values (4.44 ± 0.14 vs. 4.58 ± 0.07; t = 5.99, t = -2.58, t = -3.02, and t = -4.88, respectively; all P < 0.05). Cross-sectional VMO area and λ1 values did not differ between the two groups (t = -1.82 and t = 0.22, respectively; both P > 0.05). CONCLUSIONS: The functional status of the VMO is closely associated with recurrent patellar dislocation. MRI, especially DTI (FA, ADC, λ2, and λ3), can detect early changes in VMO function and might facilitate the noninvasive monitoring of the functional status of the VMO in patients with recurrent patellar dislocation.

Preparation and evaluation of MRI detectable poly (acrylic acid) microspheres loaded with superparamagnetic iron oxide nanoparticles for transcatheter arterial embolization.

To monitor the spatial distribution of embolic particles inside the target tissues during and after embolization, blank poly (acrylic acid) microspheres (PMs) were initially prepared by inverse suspension polymerization method and then loaded with superparamagnetic iron oxide (SPIO) nanoparticles by in situ precipitation method to obtain magnetic resonance imaging (MRI) detectable SPIO-loaded poly (acrylic acid) microspheres (SPMs). The loading of SPIO nanoparticles in SPMs was confirmed by vibrating sample magnetometer, transmission electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy and infrared spectrum, respectively. The results showed that SPMs exhibited excellent superparamagnetism and the SPIO embedded in SPMs were proved to be inverse spinel magnetite. The content of SPIO loaded in wet SPMs of subgroups of 100-300, 300-500, 500-700 and 700-900µm was measured to be 11.84±0.07, 10.20±0.05, 9.98±0.00 and 8.79±0.01mg/ml, corresponding to the weight percentage in freeze-dried SPMs to be 18.07±0.28%, 18.54±0.13%, 18.66±0.01% and 18.50±0.07%, respectively. The SPMs were spherical in shape, had smooth surface, and were within the size range of clinical demands for embolization. The compression tests indicated that SPMs were more rigid than PMs and commercially used Embospheres (P<0.01). The MRI detectability of SPMs was evaluated with the SPMs embedded in gel phantom in vitro and injected subcutaneously into the back of mice in vivo. Both the results demonstrated that the SPMs could provide distinct negative contrast enhancement and be sensitively detected by T2-weighted MR imaging. All the results show that SPMs are potential MRI detectable embolic microspheres for the future embolotherapy.

In vitro study of novel gadolinium-loaded liposomes guided by GBI-10 aptamer for promising tumor targeting and tumor diagnosis by magnetic resonance imaging.

Novel gadolinium-loaded liposomes guided by GBI-10 aptamer were developed and evaluated in vitro to enhance magnetic resonance imaging (MRI) diagnosis of tumor. Nontargeted gadolinium-loaded liposomes were achieved by incorporating amphipathic material, Gd (III) [N,N-bis-stearylamidomethyl-N'-amidomethyl] diethylenetriamine tetraacetic acid, into the liposome membrane using lipid film hydration method. GBI-10, as the targeting ligand, was then conjugated onto the liposome surface to get GBI-10-targeted gadolinium-loaded liposomes (GTLs). Both nontargeted gadolinium-loaded liposomes and GTLs displayed good dispersion stability, optimal size, and zeta potential for tumor targeting, as well as favorable imaging properties with enhanced relaxivity compared with a commercial MRI contrast agent (CA), gadopentetate dimeglumine. The use of GBI-10 aptamer in this liposomal system was intended to result in increased accumulation of gadolinium at the periphery of C6 glioma cells, where the targeting extracellular matrix protein tenascin-C is overexpressed. Increased cellular binding of GTLs to C6 cells was confirmed by confocal microscopy, flow cytometry, and MRI, demonstrating the promise of this novel delivery system as a carrier of MRI contrast agent for the diagnosis of tumor. These studies provide a new strategy furthering the development of nanomedicine for both diagnosis and therapy of tumor.