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

Journal Article · Wed Dec 01 00:00:00 EST 2010 · International Journal of Radiation Oncology, Biology and Physics

DOI:https://doi.org/10.1016/j.ijrobp.2010.02.020· OSTI ID:21499703

Schweitzer, Andrew D ^[1]; Revskaya, Ekaterina; Chu, Peter ^[1]; Pazo, Valeria ^[2]; Friedman, Matthew ^[1]; Nosanchuk, Joshua D ^[3]; Cahill, Sean ^[4]; Frases, Susana ^[5]; Casadevall, Arturo ^[3]; Dadachova, Ekaterina ^[1]

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1. Department of Nuclear Medicine, Albert Einstein College of Medicine, Bronx, NY (United States)
2. Jacobi Medical Center, Bronx, NY (United States)
3. Department of Medicine, Albert Einstein College of Medicine, Bronx, NY (United States)
4. Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY (United States)
5. Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY (United States)

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 {sup 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.

• OSTI ID: 21499703
• Journal Information: International Journal of Radiation Oncology, Biology and Physics, Vol. 78, Issue 5; Other Information: DOI: 10.1016/j.ijrobp.2010.02.020; PII: S0360-3016(10)00254-3; Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0360-3016
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
BONE MARROW
LIGHT SCATTERING
MELANIN
MELANOMAS
MICE
NANOSTRUCTURES
PARTICLES
POLYMERIZATION
RADIATION PROTECTION
RADIOIMMUNOTHERAPY
SILICA
TRANSMISSION ELECTRON MICROSCOPY
ANIMAL TISSUES
ANIMALS
BODY
CARCINOMAS
CHEMICAL REACTIONS
DISEASES
ELECTRON MICROSCOPY
EPITHELIOMAS
HEMATOPOIETIC SYSTEM
HYDROXY COMPOUNDS
IMMUNOTHERAPY
MAMMALS
MEDICINE
MICROSCOPY
MINERALS
NEOPLASMS
NUCLEAR MEDICINE
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
OXIDE MINERALS
PIGMENTS
RADIOLOGY
RADIOTHERAPY
RODENTS
SCATTERING
THERAPY
VERTEBRATES