Noncovalent Functionalization of Carbon Nanotubes with Amphiphilic Gd³⁺ Chelates: Toward Powerful T₁ and T₂ MRI Contrast Agents

An amphiphilic gadolinium (III) chelate (GdL) was synthesized from commercially available stearic acid. Aqueous solutions of the complex at different concentrations (from 1 mM to 1 μM) were prepared and adsorbed on multiwalled carbon nanotubes. The resulting suspensions were stable for several days and have been characterized with regard to magnetic resonance imaging (MRI) contrast agent applications. Longitudinal water proton relaxivities, r1, have been measured at 20, 300, and 500 MHz. The r1 values show a strong dependence on the GdL concentration, particularly at low field. The relaxivities decrease with increasing field as it is predicted by the Solomon−Bloembergen−Morgan theory. Transverse water proton relaxation times, T2, have also been measured and are practically independent of both the frequency and the GdL concentration. An in vivo feasibility MRI study has been performed at 300 MHz in mice. A negative contrast could be well observed after injection of a suspension of functionalized nanotubes into the muscle of the leg of the mouse

Mechanostereoselective One-Pot Synthesis of Functionalized Head-to-Head Cyclodextrin [3]Rotaxanes and Their Application as Magnetic Resonance Imaging Contrast Agents

A versatile, five-component, one-pot synthesis of cyclodextrin (CD) [3]­rotaxanes using copper-catalyzed azide–alkyne cycloaddition has been developed. Head-to-head [3]­rotaxanes of α-CD selectively functionalized by one or two gadolinium 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid monoamide complexes were obtained mechanostereoselectively. The magnetic resonance imaging efficiency, expressed by the longitudinal proton relaxivity of the rotaxanes, was significantly improved as compared to the functionalized CD. In vitro and in vivo preclinical studies showed a higher contrast and retention in the kidney than gadolinium 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid complex, demonstrating the potential of these rotaxanes as MRI contrast agent

Clickable-Zwitterionic Copolymer Capped-Quantum Dots for in Vivo Fluorescence Tumor Imaging

In the last decades, fluorescent quantum dots (QDs) have appeared as high-performance biological fluorescent nanoprobes and have been explored for a variety of biomedical optical imaging applications. However, many central challenges still exist concerning the control of the surface chemistry to ensure high biocompatibility, low toxicity, antifouling, and specific active targeting properties. Regarding in vivo applications, circulation time and clearance of the nanoprobe are also key parameters to control the design and characterization of new optical imaging agents. Herein, the complete design and characterization of a peptide-near-infrared-QD-based nanoprobe for biomedical optical imaging is presented from the synthesis of the QDs and the zwitterionic-azide copolymer ligand, enabling a bio-orthogonal coupling, till the final in vivo test through all the characterization steps. The developed nanoprobes show high fluorescence emission, controlled grafting rate, low toxicity, in vitro active specific targeting, and in vivo long circulating blood time. This is, to our knowledge, the first report characterizing the in vivo circulation kinetics and tumor accumulation of targeted zwitterionic QDs

KIT is required for hepatic function during mouse post-natal development-0

<p><b>Copyright information:</b></p><p>Taken from "KIT is required for hepatic function during mouse post-natal development"</p><p>http://www.biomedcentral.com/1471-213X/7/81</p><p>BMC Developmental Biology 2007;7():81-81.</p><p>Published online 5 Jul 2007</p><p>PMCID:PMC1940254.</p><p></p> New ENU-induced alleles at the Kit locus. (A) Heterozygous individuals carrying the Sco1, Sco5, Sow3 and Whc1 mutations display white spotting on the belly and a white forehead blaze while homozygotes (-/-) have a white coat color with black eyes. (B) Haplotype analysis of 114Sow3/+ mutant mice derived from the F1C3FeB6 × B6 strategy. Markers are shown with their position (Mb) from the centromere of chromosome 5 (position based on Ensembl v33) and the position of the Kit gene is shown by an arrowhead. The black and white boxes represent respectively the B6 and the C3Fe alleles. The cumulative number of mice sharing the same haploid genotype is noted at the top of each column. (C) The mutated amino-acids found in the Sco1, Sco5 alleles are located in the N-terminal hinge part of the intracellular tyrosine kinase domain of the KIT protein, at the vicinity of the T660 amino acid, mutated in the KitW-v allele, whereas the F809 modified in Whc1 is found at the level of the Mg2+ binding loop of the activation segment. (D) Sequence chromatograph spanning the Sco1, Sco5 and Whc1 mutation sites respectively in exons 12, 14 and 17 of the Kit gene compared with that of a wild-type control from the same genetic background (C3Fe). The amino-acid substitution is labeled in red. (E) Transheterozygous animals carrying the Sow3 and the KitW-v or the KitW allele exhibit a white coat color and pigmented eyes. Magnol et al. BMC Developmental Biology 2007 7:81 doi:10.1186/1471-213X-7-8

KIT is required for hepatic function during mouse post-natal development-2

<p><b>Copyright information:</b></p><p>Taken from "KIT is required for hepatic function during mouse post-natal development"</p><p>http://www.biomedcentral.com/1471-213X/7/81</p><p>BMC Developmental Biology 2007;7():81-81.</p><p>Published online 5 Jul 2007</p><p>PMCID:PMC1940254.</p><p></p>rozygous intercrosses (n = 13; n = 28; wt n = 16) reveal that mutant homozygotes are strongly affected during post-natal development compared to control littermates. () At 7.5 dpc, livers of mutants have a more yellowish color which was associated with the appearance of some white areas (white arrowhead). These alterations were never observed in wild-type (wt) littermates. () Hematoxylin and eosin, and Oil-red-O stainings reveal the swelling of hepatocytes with formation of large lipid-containing vesicles in homozygotes versus wild-type mouse littermates at 7.5 and 10.5 dpp (magnification ×40). () Staining of individuals at 7.5 dpp shows a relative increase in lipid droplets inside hepatocytes compared to wild-type (). A similar defect is observed in the liver of 7.5 dpp old mice, surviving adult homozygotes and compound mutants. () The lipid accumulation in the liver was studied by NMR during post-natal development at various ages on wt (n = 5; black) and mutant (n = 9,8,8,3; white) individuals. No statistical analysis was possible at 10.5 dpp because of the death of 6 mutants out of 9 (#), but the lipid/water ratio is still increased in mutant mice, at 10.5 dpp, in coherence with mortality scale and histology. () At 0.5 dpp, the Oil-red-O staining of liver sections from homozygous and control mice which had not yet suckled, are identical showing no accumulation of lipids. However, after breast feeding, hepatocytes from control newborns appear to stock lipids inside microvesicles at 1.5 dpp, a phenomenon that is not observed at later stages. On the contrary, in mutant mice which have suckled milk from their mother, lipids accumulation is still found in hepatic cells after 1.5 dpp

KIT is required for hepatic function during mouse post-natal development-1

<p><b>Copyright information:</b></p><p>Taken from "KIT is required for hepatic function during mouse post-natal development"</p><p>http://www.biomedcentral.com/1471-213X/7/81</p><p>BMC Developmental Biology 2007;7():81-81.</p><p>Published online 5 Jul 2007</p><p>PMCID:PMC1940254.</p><p></p>hematocrit (Hct), Mean Red Cell volume (MRCV), Mean Cell Haemoglobin Concentration (MCHC), Mean Cell Hemoglobin (MCH), Red Cell Distribution Width (RCDW), Platelet, Mean Platelet Volume (MPV) and White Blood Cells (WBC) were determined for homozygous males (, n = 5; /, n = 11; /, n = 6; /, n = 6) and compared to wild-type (wt, n = 11) individuals. Results are expressed as mean ± sem. () Testis were sectioned and stained with Hematoxylin and Eosin showing a normal appearance and organization in the and mutants. On the contrary, the seminiferous tubules of adult mutant individuals are lacunar with a complete absence of all the layers corresponding to the differentiation of spermatogonial stem cells. The β-galactosidase pattern of expression reveals that mutant mice showed no pattern of spermatogenesis compared to

KIT is required for hepatic function during mouse post-natal development-4

<p><b>Copyright information:</b></p><p>Taken from "KIT is required for hepatic function during mouse post-natal development"</p><p>http://www.biomedcentral.com/1471-213X/7/81</p><p>BMC Developmental Biology 2007;7():81-81.</p><p>Published online 5 Jul 2007</p><p>PMCID:PMC1940254.</p><p></p>ity on vibratome sections (40×) from 0.5 to 10.5 dpp, in adult, and on an eosin-stained sections (last panel). From birth to 2.5 dpp, β-galactosidase staining is found in a large number of hepatic cells, a reminiscence of the haematopoietic liver activity that takes place during late stage of embryonic development and ends after birth. As a consequence, the number of dispersed positive cells is reduced at 3.5 dpp. However, Kit expressing cells are clearly observed in the liver from 4.5 dpp to later stages and in adults. In moribund newborns at 0.5 dpp, β-galactosidase staining is weaker due to the defect in hematopoiesis during fetal development but still remained in few cells. () At 7.5 dpp expression is detected in liver whereas no expression is observed in transheterozygous and liver. Such compound heterozygotes suffer from a strong lipid steatosis as shown here for liver stained with oil-red-O (last panel). A similar staining was detected in liver (not shown)

KIT is required for hepatic function during mouse post-natal development-3

<p><b>Copyright information:</b></p><p>Taken from "KIT is required for hepatic function during mouse post-natal development"</p><p>http://www.biomedcentral.com/1471-213X/7/81</p><p>BMC Developmental Biology 2007;7():81-81.</p><p>Published online 5 Jul 2007</p><p>PMCID:PMC1940254.</p><p></p>from the plasma (; 10 individuals per genotype) of mutant and wild-type littermates at 7.5 and 10.5 dpp. Concentrations are indicated as a mean ± s.e.m and expressed as mg/g of tissue or mg/dl respectively. PL, CH, TG for plasma lipids, cholesterol, triglycerides. HDL-C and LDL-C for cholesterol associated respectively with HDL and LDL

KIT is required for hepatic function during mouse post-natal development-7

<p><b>Copyright information:</b></p><p>Taken from "KIT is required for hepatic function during mouse post-natal development"</p><p>http://www.biomedcentral.com/1471-213X/7/81</p><p>BMC Developmental Biology 2007;7():81-81.</p><p>Published online 5 Jul 2007</p><p>PMCID:PMC1940254.</p><p></p>hematocrit (Hct), Mean Red Cell volume (MRCV), Mean Cell Haemoglobin Concentration (MCHC), Mean Cell Hemoglobin (MCH), Red Cell Distribution Width (RCDW), Platelet, Mean Platelet Volume (MPV) and White Blood Cells (WBC) were determined for homozygous males (, n = 5; /, n = 11; /, n = 6; /, n = 6) and compared to wild-type (wt, n = 11) individuals. Results are expressed as mean ± sem. () Testis were sectioned and stained with Hematoxylin and Eosin showing a normal appearance and organization in the and mutants. On the contrary, the seminiferous tubules of adult mutant individuals are lacunar with a complete absence of all the layers corresponding to the differentiation of spermatogonial stem cells. The β-galactosidase pattern of expression reveals that mutant mice showed no pattern of spermatogenesis compared to

KIT is required for hepatic function during mouse post-natal development-5

<p><b>Copyright information:</b></p><p>Taken from "KIT is required for hepatic function during mouse post-natal development"</p><p>http://www.biomedcentral.com/1471-213X/7/81</p><p>BMC Developmental Biology 2007;7():81-81.</p><p>Published online 5 Jul 2007</p><p>PMCID:PMC1940254.</p><p></p>ctangle) compare to wild type (filled rectangle) while is significantly downregulated at 1.5 dpp. At 10.5 dpp, the expression level of , and is low in mutant compare to wild-type livers whereas the expression of is not affected. All the data were normalized as described in the Materials and Methods and were subjected to statistical analysis (Fischer and Student t tests, * for p < 0.05 and ** for p < 0.01)