Des nanoparticules pour protéger la moelle osseuse

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Des nanoparticules pour protéger la moelle osseuse

Message par Stéphane » ven. avr. 30, 2010 6:54 pm

Certains traitements contre le cancer reposent sur des radiations ionisantes, qui peuvent détruire les cellules malignes mais aussi endommager les cellules saines, comme celles de la moelle osseuse. Un groupe de chercheurs de l’Université Yeshiva a trouvé une parade prometteuse pour protéger les cellules de moelle : des nanoparticules enduites de mélanine.

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Bull
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Message par Bull » ven. avr. 30, 2010 7:31 pm

Vi monsieur,

Abstract (1) ci-dessous.
Je connais un des groupes qui a travaillé sur ce projet.
Je pense que ce n'est publié "que" dans un bon journal de spécialité car le concept n'est pas totalement nouveau. Voir par exemple ce papier que les mêmes (enfin la plupart) ont déjà récemment publié dans PLoS One (2)


Ceci dit, amha hein, c'est vraiment très "joli" comme approche.

1)
Int J Radiat Oncol Biol Phys. 2010 Apr 24. [Epub ahead of print]

Melanin-Covered Nanoparticles for Protection of Bone Marrow During Radiation Therapy of Cancer.

Schweitzer AD, Revskaya E, Chu P, Pazo V, Friedman M, Nosanchuk JD, Cahill S, Frases S, Casadevall A, Dadachova E.

Department of Nuclear Medicine, Albert Einstein College of Medicine, Bronx, NY, United States; Howard Hughes Medical Institute-Medical Fellows Program, Chevy Chase, MD, United States; The Mount Sinai School of Medicine, New York, NY, United States.
Abstract

PURPOSE: Protection of bone marrow against radiotoxicity during radioimmunotherapy and in some cases external beam radiation therapy such as hemi-body irradiation would permit administration of significantly higher doses to tumors, resulting in increased efficacy and safety of treatment. Melanin, a naturally occurring pigment, possesses radioprotective properties. We hypothesized that melanin, which is insoluble, could be delivered to the bone marrow by intravenously administrated melanin-covered nanoparticles (MNs) because of the human body's "self-sieving" ability, protecting it against ionizing radiation. METHODS AND MATERIALS: The synthesis of MNs was performed via enzymatic polymerization of 3,4-dihydroxyphenylalanine and/or 5-S-cysteinyl-3,4-dihydroxyphenylalanine on the surface of 20-nm plain silica nanoparticles. The biodistribution of radiolabeled MNs in mice was done at 3 and 24 h. Healthy CD-1 mice (Charles River Laboratories International, Inc., Wilmington, MA) or melanoma tumor-bearing nude mice were given MNs intravenously, 50 mg/kg of body weight, 3 h before either whole-body exposure to 125 cGy or treatment with 1 mCi of (188 )Re-labeled 6D2 melanin-binding antibody. RESULTS: Polymerization of melanin precursors on the surface of silica nanoparticles resulted in formation of a 15-nm-thick melanin layer as confirmed by light scattering, transmission electron microscopy, and immunofluorescence. The biodistribution after intravenous administration showed than MN uptake in bone marrow was 0.3% and 0.2% of injected dose per gram at 3 and 24 h, respectively, whereas pre-injection with pluronic acid increased the uptake to 6% and 3% of injected dose per gram, respectively. Systemic MN administration reduced hematologic toxicity in mice treated with external radiation or radioimmunotherapy, whereas no tumor protection by MNs was observed. CONCLUSIONS: MNs or similar structures provide a novel approach to protection of bone marrow from ionizing radiation based on prevention of free radical formation by melanin. Copyright © 2010 Elsevier Inc. All rights reserved.
2)
PLoS One. 2009 Sep 30;4(9):e7229.
Physico-chemical evaluation of rationally designed melanins as novel nature-inspired radioprotectors.

Schweitzer AD, Howell RC, Jiang Z, Bryan RA, Gerfen G, Chen CC, Mah D, Cahill S, Casadevall A, Dadachova E.

Department of Nuclear Medicine, Albert Einstein College of Medicine, New York, New York, United States of America.
Abstract

BACKGROUND: Melanin, a high-molecular weight pigment that is ubiquitous in nature, protects melanized microorganisms against high doses of ionizing radiation. However, the physics of melanin interaction with ionizing radiation is unknown. METHODOLOGY/PRINCIPAL FINDINGS: We rationally designed melanins from either 5-S-cysteinyl-DOPA, L-cysteine/L-DOPA, or L-DOPA with diverse structures as shown by elemental analysis and HPLC. Sulfur-containing melanins had higher predicted attenuation coefficients than non-sulfur-containing melanins. All synthetic melanins displayed strong electron paramagnetic resonance (2.14.10(18 ), 7.09.10(18 ), and 9.05.10(17) spins/g, respectively), with sulfur-containing melanins demonstrating more complex spectra and higher numbers of stable free radicals. There was no change in the quality or quantity of the stable free radicals after high-dose (30,000 cGy), high-energy ((137)Cs, 661.6 keV) irradiation, indicating a high degree of radical stability as well as a robust resistance to the ionizing effects of gamma irradiation. The rationally designed melanins protected mammalian cells against ionizing radiation of different energies. CONCLUSIONS/SIGNIFICANCE: We propose that due to melanin's numerous aromatic oligomers containing multiple pi-electron system, a generated Compton recoil electron gradually loses energy while passing through the pigment, until its energy is sufficiently low that it can be trapped by stable free radicals present in the pigment. Controlled dissipation of high-energy recoil electrons by melanin prevents secondary ionizations and the generation of damaging free radical species.

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