Superparamagnetic Nanoparticles for Atherosclerosis Imaging

The production of magnetic nanoparticles of utmost quality for biomedical imaging requires several steps, from the synthesis of highly crystalline magnetic cores to the attachment of the different molecules on the surface. This last step probably plays the key role in the production of clinically useful nanomaterials. The attachment of the different biomolecules should be performed in a defined and controlled fashion, avoiding the random adsorption of the components that could lead to undesirable byproducts and ill-characterized surface composition. In this work, we review the process of creating new magnetic nanomaterials for imaging, particularly for the detection of atherosclerotic plaque, in vivo. Our focus will be in the different biofunctionalization techniques that we and several other groups have recently developed. Magnetic nanomaterial functionalization should be performed by chemoselective techniques. This approach will facilitate the application of these nanomaterials in the clinic, not as an exception, but as any other pharmacological compound.The authors thank the Spanish Ministry of Science (SAF2011-25445), the Comunidad de Madrid (S2010/BMD-2326, Inmunothercan-CM, NANOCOPD-CIBERES-CIBERBBN-SEPAR), and the EU 7th Framework Program (FP7-PEOPLE-ITN-264864 Pinet and FP7-PEOPLE-2013-ITN CardioNext).S

Phase I study on docetaxel and ifosfamide in patients with advanced solid tumours.

Docetaxel and ifosfamide have shown significant activity against a variety of solid tumours. This prompted a phase I trial on the combination of these drugs. This phase I study was performed to assess the feasibility of the combination, to determine the maximum tolerated dose (MTD) and the side effects, and to propose a safe schedule for further phase II studies. A total of 34 patients with a histologically confirmed solid tumour, who were not pretreated with taxanes or ifosfamide and who had received no more than one line of chemotherapy for advanced disease were entered into the study. Treatment consisted of docetaxel given as a 1-h infusion followed by ifosfamide as a 24-h infusion (schedule A), or ifosfamide followed by docetaxel (schedule B) every 3 weeks. Docetaxel doses ranged from 60 to 85 mg m(-2) and ifosfamide doses from 2.5 to 5.0 g m(-2). Granulocytopenia grade 3 and 4 were common (89%), short lasting and ifosfamide dose dependent. Febrile neutropenia and sepsis occurred in 17% and 2% of courses respectively. Non-haematological toxicities were mild to moderate and included alopecia, nausea, vomiting, mucositis, diarrhoea, sensory neuropathy, skin and nail toxicity and oedema. There did not appear to be any pharmacokinetic interaction between docetaxel and ifosfamide. One complete response (CR) (soft tissue sarcoma) and two partial responses (PRs) were documented. A dose of 75 mg m(-2) of docetaxel combined with 5.0 g m(-2) ifosfamide appeared to be manageable. Schedule A was advocated for further treatment

Phosphatidylcholine-coated iron oxide nanomicelles for in vivo prolonged circulation time with an antibiofouling protein corona

We report the synthesis of micellar phosphatidylcholine-coated superparamagnetic iron oxide nanoparticles as a new long circulation contrast agents for magnetic resonance imaging. Oleic acid-coated Fe3 O4 nanoparticles were first prepared through thermal degradation and then encapsulated into small clusters with a phosphatidylcholine coating to obtain hydrophilic nanomicelles. A thorough characterization confirmed the chemical nature of the coating and the excellent colloidal stability of these nanomicelles in aqueous media. Magnetization and relaxivity properties proved their suitability as magnetic resonance imaging (MRI) contrast agent and in vitro cell viability data showed low toxicity. Vascular lifetime and elimination kinetics in the liver were assessed by blood relaxometry and by in vivo MRI in rats and compared with "control" particles prepared with a polyethylene glycol derivative. These micellar particles had a lifetime in blood of more than 10 h, much longer than the control nanoparticles (≈2 h), which is remarkable considering that the coating molecule is a small biocompatible zwitterionic phospholipid. The protein corona was characterized after incubation with rat serum at different times by high-throughput proteomics, showing a higher proportion of bound apolipoproteins and other dysopsonins for the phosphatidylcholine particles. The antibiofouling properties of this corona and its resistance to the adsorption of proteins corroborate the observed enhanced stability and prolonged systemic circulation.This study is supported by a grant from FP7 Marie Curie, Pulmonary imaging network (PINET), by Fundacio La Maratode TV3 (70/C/2012) and by a grant from the Comunidad de Madrid (S2010/BMD-2326, Inmunothercan-CM) and by Spanish Economy Ministry (MAT2013-47303-P). We thank E. Urones (Centro Nacional de Microscopia de la Universidad Complutense de Madrid) for the transmission electronic microscopy imaging; P. Morales (Instituto de Ciencia de Materiales de la Universidad Autonoma de Madrid) for the thermogravimetric and magnetization analysis and B. Salinas (Fundacion Centro Nacional de Investigaciones Cardiovasculares and CIBER de Enfermedades Respiratorias) for the TEM picture of oleic acid coated Fe3 O4. The authors declare no competing financial interests.S

A phase II study of docetaxel in patients with metastatic squamous cell carcinoma of the head and neck

This study was designed to evaluate the activity, safety and tolerance of docetaxel (D) in a selected population with metastatic squamous cell carcinoma of the head and neck (SCCHN). Twenty-four patients with no prior palliative therapy were enrolled and received D 100 mg m−2 by 1 h of infusion, every 3 weeks. All but two patients had been evaluated for efficacy on lung metastatic sites. No prophylactic administration of anti-emetics or growth factors was given. A pharmacokinetic study was performed in 22 patients. Twenty-one patients were assessable for response and 24 for toxicity. One hundred and four cycles were administered with a median of 4.5 (range 1–9) per patient. The median cumulative dose was 449 mg m−2. Partial responses were achieved in five patients with a median duration of 18.7 weeks (range 13.1–50.3). The overall response rate was 20.8% with a median duration of 11.0 weeks (range 2.4–52.6). The most frequent side-effect was neutropenia (79.2% grade IV) but with a short duration (median 4 days) and no febrile neutropenia. The incidence of moderate/severe fluid retention was 29.2% with one treatment discontinuation. Other toxicities (all grades) were common (skin 75%, asthenia 50%, infection 29.2%, nausea 16.7%, diarrhoea 12.5%, stomatitis 16.7%, vomiting 8.3% and HSR 8.3%). A mean clearance of 19.6 l h−1 m−2 and an area under the curve of 6.00 μg ml−1 h−1 was found in the pharmacokinetic analysis. Docetaxel is active in this selected population with metastatic SCCHN, with a good tolerance. © 1999 Cancer Research Campaig

Heavy Ions Irradiation Effects On Magnetization Of Tl2ba2cacu2o8 And Tlba2cacu2o7 Single Crystals

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Magnetization measurements were performed as a function of magnetic field and time in Tl2Ba2CaCu2O8 and TlBa2CaCu2O7 single crystals to study the effects of high energy Xe ion irradiation. The effective pinning energies at 6 K and 40 K have been evaluated from magnetic relaxation measurements. The activation energies are hardly changed after irradiation. The study of magnetization hysteresis shows that an irradiation fluence of 2 × 1011 ions cm-2 enhanced hysteresis at 6 K in both crystals. But a fluence of 1012 ions cm-2 was detrimental for the 2212 sample which is the most sensitive to heavy ion irradiation damage in the Tl-cuprate family. The magnetic hysteresis at 70 K after irradiation is more drastically increased than at 6 K. This spectacular modification is interpreted by a recovery of the 3D character of the flux line lattice. © 1992.13427928507/57630-5; FAPESP; Simons Foundation; 2013/09850-7; FAPESP; Simons Foundation; DMR-1005751; NSF; Simons Foundation; PHYS-1066293; NSF; Simons Foundation; SF; Simons FoundationFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Umezawa, Crabtree, Liu, Weber, Kwok, Nunez, Moran, Claus, (1987) Phys. Rev. B, 36, p. 7151van Dover, Gyorgy, White, Schneemeyer, Felder, Wasczak, (1990) Appl. Phys. Lett., 56, p. 2681Civale, Warwick, McElfresh, Worthington, Malozemoff, Holzberg, Thompson, Kirk, (1990) Phys. Rev. Lett., 65, p. 1164Kritscha, Sauerzopf, Weber, Crabtree, Chang, Jiang, Flux Pinning Enhancement and Shift of the Irreversibility Line by Fast Neutron Irradiation of Single Crystal Bi2Sr2CaCu2O8 (1990) Europhysics Letters (EPL), 12, p. 179Vichery, Rullier-Albenque, Pascard, Konczylowski, Kormann, Favrot, Collin, (1989) Physica C, 159, p. 697Bourgault, Bouffard, Toulemonde, Groult, Provost, Studer, Nguyen, Raveau, (1989) Phys. Rev. B, 39, p. 6549Bourgault, Hervieu, Bouffard, Groult, Raveau, (1989) Nucl. Instrum. Methods B, 42, p. 61Hardy, Groult, Hervieu, Provost, Raveau, Bouffard, (1991) Nucl. Instrum. Methods B, 54, p. 472Venturini, Barbour, Ginley, Baughman, Morosin, (1990) Appl. Phys. Lett., 56, p. 2456Osborn, (1945) Phys. Rev., 67, p. 351Yeshurun, Malozemoff, Holtzberg, Dinger, (1988) Phys. Rev. B, 38, p. 11828Campbell, Fruchter, Cabanel, (1990) Phys. Rev. Lett., 64, p. 1561Xu, Suenaga, Moodenbaugh, Welch, (1989) Phys. Rev. B, 40, p. 10882Stollman, Dam, Emmen, Pankert, (1989) Physica C, 161, p. 444Beasley, Labush, Welb, (1969) Phys. Rev., 181, p. 682Martin, Maignan, Provost, Michel, Hervieu, Tournier, Raveau, (1990) Physica C, 168, p. 8Hardy, Groult, Provost, Hervieu, Raveau, Bouffard, (1991) Physica C, 178, p. 255Raveau, Hervieu, Michel, Provost, (1989) Mater. Sci. Eng., 109 A, p. 281Hardy, Hervieu, Groult, Provost, (1991) Radiation Effects and Defects in Solids, , in the pressKopylev, Schegolev, Togonidze, Magnetization curves and low critical fields of Tl2Ba2CaCu2Ox single crystals (1989) Physica C: Superconductivity, 162-164, p. 1143Kopylev, Koshelev, Schegolev, Togonidze, The role of surface effects in magnetization of high-Tc superconductors (1990) Physica C: Superconductivity, 170, p. 291Kes, Aarts, van den Berg, van der Beek, Mydoch, (1989) Supercond. Sci. Technol., 1, p. 242Palstra, Batlogg, Scheemeyer, Wasczak, (1991) Phys. Rev. B, 43, p. 3756de Rango, Giordanengo, Tournier, Sulpice, Chaussy, Deutscher, Genicon, Raveau, The « irreversibility line » of Bi2-xPbxSr2Ca2Cu3O10 : a possible breakdown of an intrinsic proximity effect (1989) Journal de Physique, 50, p. 2857Raveau, Michel, Provost, Hervieu, The nature and the role of rock salt-type layers in superconductive layered copper oxides (1990) Solid State Ionics, 40-41, p. 785. , 1st ednV.Z. Kresin, S.A. Wolf and G. Deutscher, PreprintV. Hardy, J. Provost, D. Groult, M. Hervieu, B. Raveau, S. Durcok, E. Pollert, J.-C. Frison, J.-P. Chaminade and M. Pouchard, Physica C, accepted for publicationKonczykowski, Rullier-Albenque, Yacoby, Shaulov, Yeshurun, Lejay, (1991) Phys. Rev. B, 44, p. 7167Civale, Marwick, Worthington, Kirk, Thompson, Krusin-Elbaum, Sun, Holtzberg, (1991) Phys. Rev. Lett., 67, p. 64