Effects of core size and PEG coating layer of iron oxide nanoparticles on the distribution and metabolism in mice.
Effects of core size and PEG coating layer of iron oxide nanoparticles on the distribution and metabolism in mice.
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DOI：
10.2147/ijn.s165451
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发表时间：
2018
影响因子：
8
通讯作者：
Fan H
中科院分区：
文献类型：
--
作者：
Xue W;Liu Y;Zhang N;Yao Y;Ma P;Wen H;Huang S;Luo Y;Fan H
聚乙二醇化功能纳米粒在体内的分布对于确定其在纳米医学中的成像功能和治疗效果至关重要。然而，关于纳米粒子的核大小和表面对生物分布的影响的报道却是相互矛盾的。为了澄清这种模棱两可的理解，我们以氧化铁纳米颗粒(IONPs)为模型系统，研究了核大小和聚乙二醇分子量对小鼠体内分布的影响。制备了三种聚乙二醇化的IONP，包括14 nm IONP@PEG2000、14 nm IONP@PEG5000和22 nm IONP@PEG5000，其流体力学尺寸分别为26、34和81 nm。对其血药动学和组织分布进行了详细的研究。结果表明，决定IONPs半衰期的主要因素是聚乙二醇层，而不是核的尺寸。具体地说，聚乙二醇层的相对分子质量越大，半衰期越长。这些聚乙二醇化的IONPs主要通过肝脏清除排泄。虽然聚乙二醇单分子层是决定清除率的关键因素，但核尺寸影响清除率。完整的血细胞计数分析和组织病理学表明聚乙二醇化的IONPs具有良好的生物相容性，可用于未来的临床试验。
In vivo distribution of polyethylene glycol (PEG)ylated functional nanoparticles is vital for determining their imaging function and therapeutic efficacy in nanomedicine. However, contradictory results have been reported regarding the effect of core size and PEG surface of the nanoparticles on biodistribution. To clarify this ambiguous understanding, using iron oxide nanoparticles (IONPs) as a model system, we investigated the effect of core size and PEG molecule weights on in vivo distribution in mice. Three PEGylated IONPs, including 14 nm IONP@PEG2,000, 14 nm IONP@PEG5,000, and 22 nm IONP@PEG5,000, were prepared with a hydrodynamic size of 26, 34, and 81 nm, respectively. The blood pharmacokinetics and tissue distribution were investigated in detail. The results indicated that the PEG layer, rather than core size, played a dominant role in determining the half-life time of IONPs. Specifically, increased molecular weight of the PEG layer led to a longer half-life time. These PEGylated IONPs were mainly excreted by liver clearance. While the PEG molecular layer constituted the key factor to determine the clearance ratio, core size affected the clearance rate. Complete blood count analysis and histopathology suggested excellent biocompatibility of PEGylated IONPs for future clinical trials.