MELANIN-COVERED NANOPARTICLES FOR PROTECTION OF BONE MARROW DURING RADIATION THERAPY OF CANCER

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 mar row by intravenously administrated melanin-covered nanoparticles (MNs) because of the human body's self-sreving ability, protecting it against ionizing radiation Methods and Materials The synthesis of MNs was performed via enzymatic polymerization of 3,4-dihydroxyphe nylalamne and/or 5 S cystelnyl 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 mC(1) of Re-188 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 03% 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 (C) 2010 Elsevier Inc