Melanin-covered nanoparticles for protection of bone marrow during radiation therapy of cancer.
Melanin-covered nanoparticles for protection of bone marrow during radiation therapy of cancer.
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DOI：
10.1016/j.ijrobp.2010.02.020
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发表时间：
2010-12-01
影响因子：
7
通讯作者：
Dadachova, Ekaterina
中科院分区：
文献类型：
--
作者：
Schweitzer, Andrew D.;Revskaya, Ekaterina;Chu, Peter;Pazo, Valeria;Friedman, Matthew;Nosanchuk, Joshua D.;Cahill, Sean;Frases, Susana;Casadevall, Arturo;Dadachova, Ekaterina
在放射免疫治疗和某些情况下的外部射束放射治疗（如半身照射）期间保护骨髓免受放射毒性，将允许对肿瘤给予显著更高的剂量，从而提高治疗的疗效和安全性。黑色素是一种天然存在的色素，具有辐射防护特性。我们假设，黑色素，这是不溶性的，可以通过静脉注射黑色素覆盖的纳米粒子（MN），因为人体的“自我筛选”能力，保护它免受电离辐射传递到骨髓。MN的合成是通过在20 nm普通二氧化硅纳米颗粒表面上酶促聚合3，4-二羟基苯丙氨酸和/或5-S-半胱氨酰-3，4-二羟基苯丙氨酸来进行的。在3和24 h进行放射性标记MN在小鼠中的生物分布。健康CD-1小鼠（Charles River Laboratories International，Inc.，威尔明顿，MA）或荷黑色素瘤的裸鼠在全身暴露于125 cGy或用1 mCi的188 Re标记的6D2黑色素结合抗体处理之前3小时静脉内给予MN，50 mg/kg体重。通过光散射、透射电子显微镜和免疫荧光证实，二氧化硅纳米颗粒表面上的黑色素前体聚合导致形成15 nm厚的黑色素层。静脉给药后的生物分布显示，骨髓中MN的摄取量在3和24 h分别为注射剂量的0.3%和0.2%/g，而预先注射普朗尼克酸使摄取量分别增加至注射剂量的6%和3%/g。全身MN给药降低了用外部辐射或放射免疫治疗的小鼠的血液毒性，而没有观察到MN的肿瘤保护作用。MN或类似结构提供了一种基于防止黑色素形成自由基来保护骨髓免受电离辐射的新方法。
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. 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. 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. 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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影响因子：
4
作者：
HILL, HZ
通讯作者：
HILL, HZ
DOI：
10.1073/pnas.0406180101
发表时间：
2004-10-12
影响因子：
11.1
作者：
Dadachova, E;Nosanchuk, JD;Casadevall, A
通讯作者：
Casadevall, A
影响因子：
3.7
作者：
PAJAK, S;HOPWOOD, LE;HATCHELL, MC
通讯作者：
HATCHELL, MC
影响因子：
4
作者：
Small, W
通讯作者：
Small, W
影响因子：
3.5
作者：
PORTER, CJH;MOGHIMI, SM;DAVIS, SS
通讯作者：
DAVIS, SS