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 188Re-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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1494-1502 |
| Number of pages | 9 |
| Journal | International Journal of Radiation Oncology Biology Physics |
| Volume | 78 |
| Issue number | 5 |
| DOIs | |
| State | Published - Dec 1 2010 |
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Keywords
- Bone marrow
- Melanin
- Nanoparticles
- Radiation protection
- Radioimmunotherapy
ASJC Scopus subject areas
- Oncology
- Radiology Nuclear Medicine and imaging
- Radiation
- Cancer Research
Cite this
Melanin-covered nanoparticles for protection of bone marrow during radiation therapy of cancer. / Schweitzer, Andrew D.; Revskaya, Ekaterina; Chu, Peter; Pazo, Valeria; Friedman, Matthew; Nosanchuk, Joshua D.; Cahill, Sean M.; Frases, Susana; Casadevall, Arturo; Dadachova, Ekaterina.
In: International Journal of Radiation Oncology Biology Physics, Vol. 78, No. 5, 01.12.2010, p. 1494-1502.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Melanin-covered nanoparticles for protection of bone marrow during radiation therapy of cancer
AU - Schweitzer, Andrew D.
AU - Revskaya, Ekaterina
AU - Chu, Peter
AU - Pazo, Valeria
AU - Friedman, Matthew
AU - Nosanchuk, Joshua D.
AU - Cahill, Sean M.
AU - Frases, Susana
AU - Casadevall, Arturo
AU - Dadachova, Ekaterina
PY - 2010/12/1
Y1 - 2010/12/1
N2 - 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 188Re-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.
AB - 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 188Re-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.
KW - Bone marrow
KW - Melanin
KW - Nanoparticles
KW - Radiation protection
KW - Radioimmunotherapy
UR - http://www.scopus.com/inward/record.url?scp=78549234658&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=78549234658&partnerID=8YFLogxK
U2 - 10.1016/j.ijrobp.2010.02.020
DO - 10.1016/j.ijrobp.2010.02.020
M3 - Article
C2 - 20421152
AN - SCOPUS:78549234658
VL - 78
SP - 1494
EP - 1502
JO - International Journal of Radiation Oncology Biology Physics
JF - International Journal of Radiation Oncology Biology Physics
SN - 0360-3016
IS - 5
ER -