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.
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Authors | Andrew D Schweitzer, Ekaterina Revskaya, Peter Chu, Valeria Pazo, Matthew Friedman, Joshua D Nosanchuk, Sean Cahill, Susana Frases, Arturo Casadevall, Ekaterina Dadachova |
Journal | International journal of radiation oncology, biology, physics
(Int J Radiat Oncol Biol Phys)
Vol. 78
Issue 5
Pg. 1494-502
(Dec 01 2010)
ISSN: 1879-355X [Electronic] United States |
PMID | 20421152
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
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Copyright | Copyright © 2010 Elsevier Inc. All rights reserved. |
Chemical References |
- Drug Carriers
- Melanins
- Radiation-Protective Agents
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Topics |
- Animals
- Bone Marrow
(metabolism, radiation effects)
- Drug Carriers
(chemical synthesis, pharmacokinetics)
- Magnetic Resonance Spectroscopy
- Melanins
(administration & dosage, chemical synthesis, pharmacokinetics)
- Melanoma
(metabolism, radiotherapy)
- Mice
- Mice, Nude
- Microscopy, Electron, Transmission
- Nanoparticles
(administration & dosage)
- Radiation Injuries, Experimental
(prevention & control)
- Radiation-Protective Agents
(administration & dosage, chemical synthesis, pharmacokinetics)
- Radioimmunotherapy
(adverse effects)
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