目的 检测羟基磷灰石纳米颗粒(HANPs)在体内的分布情况,为其体内生物安全性评价提供参考。方法 在氨基化表面改性的基础上,对羟基磷灰石纳米颗粒进行125I标记,将125I标记的羟基磷灰石纳米颗粒注射到动物体内,通过放射免疫γ计数仪检测给药后30 d内体内主要组织的放射性计数,以每克组织含百分比注射剂量(%ID·g-1)评价羟基磷灰石纳米颗粒在各组织中分布情况。结果 肺、肝脏和脾脏是羟基磷灰石纳米颗粒体内主要分布组织。在给药后1 d,组织蓄积量均超过5%ID·g-1;在给药后30 d内,羟基磷灰石纳米颗粒在肺组织中的蓄积量发生明显下降,而在肝脏和脾脏中则下降缓慢,蓄积量仍维持在2% ID·g-1以上。结论 本实验结果表明,肺、肝脏和脾脏是羟基磷灰石纳米颗粒体内生物安全性评价应重点关注的效应组织。
Abstract
OBJECTIVE To investigate the in vivo tissue distribution of hydroxyapatite nanoparticles (HANPs) and provide important information for the in vivo biosafety evaluation of HANPs. METHODS The HANPs were modified with aminopropyltriethoxysilane (APTS) to introduce amino groups on the surface. The modified HANPs were labeled with 125I and injected into mice. A γ-counter was used to quantitatively assess the radioactivity of the tissues. The accumulation of HANPs in the tissues was expressed as the percentage injected dose per gram tissue (%ID·g-1). RESULTS The HANPs mainly accumulated in the lung, liver, and spleen. One day post-injection, the accumulation in these tissues was over 5% ID·g-1. During 30 d after the injection, the accumulation of HANPs in the lung decreased quickly, while the accumulation in the liver and spleen reduced moderately and maintained at more than 2%ID·g-1. CONCLUSION This study indicates that lung, liver and spleen are the main tissues for the in vivo biosafety evaluation of HANPs.
关键词
羟基磷灰石纳米颗粒 /
125I标记 /
组织分布 /
生物安全性
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Key words
hydroxyapatite nanoparticle /
125I lebelling /
tissue distribution /
biosafety
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中图分类号：
R944
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参考文献
[1] XIA T, LI N, NEL A E. Potential health impact of nanoparticles. Annu Rev Public Health, 2009, 30:137-150. [2] DREHER K L. Health and environmental impact of nanotechnology:Toxicological assessment of manufactured nanoparticles. Toxicol Sci, 2004, 77(1):3-5. [3] LIAO S S, CUI F Z. In vitro and in vivo degradation of mineralized collagen-based composite scaffold:Nanohydroxyapatite/collagen/poly(L-lactide) . Tiss Eng, 2004, 10 (1-2):73-80. [4] WANG X, LI Y, WEI J, et al. Development of biomimetic nano-hydroxyapatite/poly(hexamethylene adipamide composites. Biomaterials, 2002, 23 (24):4787-4791. [5] YOSHIKAWA H, MYOUI A. Bone tissue engineering with porous hydroxyapatite ceramics. J Artif Organs, 2005, 8 (3):131-136. [6] SMITH G P, GINGRICH T R. Hydroxyapatite chromatography of phage-display virions. Biotechniques, 2005, 39 (6):879-884. [7] MIZUSHIMA Y, IKOMA T, TANAKA J, et al. Injectable porous hydroxyapatite microparticles as a new carrier for protein and lipophilic drugs. J Controlled Release, 2006, 110 (2):260-265. [8] GUANGPING X, CHEN W, JIAO S, et al. Tissue distribution and excretion of intravenously administered titanium dioxide nanoparticles. Toxicol Lett, 2011,205(1):55-61. [9] HE X, NIE H, WANG K, et al. In vivo study of biodistribution and urinary excretion of surface-modified silica nanoparticles. Anal Chem, 2008, 80(24):9597-9603. [10] FABIAN E, LANDSIEDEL R, MA-HOCK L, et al. Tissue distribution and toxicity of intravenously administered titanium dioxide nanoparticles in rats. Arch Toxicol, 2008, 82 (3):151-157. [11] VEERAREDDY P R, VOBALABOINA V. Pharmacokinetics and tissue distribution of piperine lipid nanospheres. Pharmazie, 2008, 63 (5):352-355. [12] YANG Z, LEON J, MARTIN M, et al. Pharmacokinetics and biodistribution of near-infrared fluorescence polymeric nanoparticles. Nanotechnology, 2009, 20(16):165101. [13] XIE G P, SUN J, ZHONG G, et al. Biodistribution and toxicity of intravenously administered silica nanoparticles in mice. Arch Toxicol, 2010, 84(3):183-190. [14] SUN J, XIE G. Tissue distribution of intravenously administrated hydroxyapatite nanoparticles labeled with 125I. J Nanosci Nanotechnol, 2011,11 (12):10996-11000. [15] LI S D, HUANG L. Pharmacokinetics and biodistribution of nanoparticles. Mol Pharm, 2008, 5 (4):496-504. [16] OPANASOPIT P, NISHIKAWA M, HASHIDA M. Factors affecting drug and gene delivery:Effects of interaction with blood components. Crit Rev Ther Drug Carrier Syst, 2002, 19 (3):191-233. [17] GAO H, SHI W, FREUND L B. Mechanics of receptor-mediated endocytosis. Proc Natl Acad Sci USA, 2005, 102 (27):9469-9474. [18] CHITHRANI B D, GHAZANI A A, CHAN W C. Determining the size and shape dependence of gold nanoparticle uptake into mammalian cells. Nano Lett,2006, 6 (4):662-668. [19] NAKAI T, KANAMORI T, SANDO S, et al. Remarkably size-regulated cell invasion by artificial viruses. Saccharide-dependent self-aggregation of glycoviruses and its consequences in glycoviral gene delivery. J Am Chem Soc,2003,125 (28):8465-8475. [20] CHITHRANI B D, CHAN W C. Elucidating the mechanism of cellular uptake and removal of protein-coated gold nanoparticles of different sizes and shapes. Nano Lett,2007,7 (6):1542-1550. [21] BAO G, BAO X R. Shedding light on the dynamics of endocytosis and viral budding. Proc Natl Acad Sci USA,2005,102 (29):9997-9998. [22] DE WOLF H K, SNEL C J, VERBAAN F J, et al. Effect of cationic carriers on the pharmacokinetics and tumor localization of nucleic acids after intravenous administration. Int J Pharm,2007,331 (2):167-175.
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脚注
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基金
浙江省自然科学基金资助项目(Y4110665);浙江省公益技术应用研究项目(2012C33115)
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