Pharmacokinetics and biodistribution of near-infrared fluorescence polymeric nanoparticles.

Pharmacokinetics and biodistribution of near-infrared fluorescence polymeric nanoparticles.
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DOI:
10.1088/0957-4484/20/16/165101
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发表时间:
2009-04-22
期刊:
影响因子:
3.5
通讯作者:
Li C
Li C
中科院分区:
材料科学3区
文献类型:
--
作者:
Yang Z;Leon J;Martin M;Harder JW;Zhang R;Liang D;Lu W;Tian M;Gelovani JG;Qiao A;Li C

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利用聚合纳米颗粒作为近红外(NIR)荧光染料的载体用于癌症诊断的兴趣越来越大。然而,在全身给药后,纳米颗粒有效地递送到肿瘤受到各种生物屏障的限制。在本研究中,我们研究了聚乙二醇包被的亚纳米级聚合物纳米颗粒(直径<100 nm)在荷瘤小鼠体内的药代动力学、生物分布和肿瘤摄取。为了便于我们的研究,这些粒子被标记为γ发射器铟-111。我们发现,两种具有相同尺寸(~20 nm)和化学成分但结构不同(即水凝胶与核壳纳米atex)的NIRF纳米颗粒,或具有不同尺寸(20、30和60 nm)的相同核壳纳米atex颗粒,具有不同的血液循环时间、生物分布和肿瘤摄取。有趣的是,肿瘤对纳米atex颗粒的摄取与其血液停留时间相关(R2 = 0.95),但纳米凝胶和纳米atex颗粒之间没有类似的相关性(R2 = 0.05)。这些结果表明,血液循环时间和纳米颗粒的水化程度在纳米颗粒的肿瘤摄取中起重要作用。静脉给药后,这些NIRF纳米颗粒的血液循环延长,可以通过γ-闪烁成像和光学成像清晰地显示肿瘤。更好地了解纳米颗粒的特性如何影响其在体内的行为,是设计适合分子成像应用和高效肿瘤递送的NIRF纳米颗粒的重要一步。
There has been increased interest in the use of polymeric nanoparticles as carriers for near-infrared (NIR) fluorescence dyes for cancer diagnosis. However, efficient delivery of nanoparticles to the tumors after systemic administration is limited by various biobarriers. In this study, we investigated the pharmacokinetics, biodistribution, and tumor uptake of sub-nanometer sized polymeric nanoparticles (<100 nm in diameter) coated with polyethylene glycol in tumor-bearing mice. To facility our studies, these particles were labeled with gamma emitter indium-111. We found that two NIRF nanoparticles having the same size (~20 nm) and chemical composition but different structures (i.e., hydrogel vs. core-shell nanolatex), or the same core-shell nanolatex particles with different sizes (20, 30, and 60 nm), had different blood circulation times, biodistribution, and tumor uptake. Interestingly, the tumor uptake of the nanolatex particles correlated well with their blood residence times (R2 = 0.95), but similar correlations were not found between nanogel and nanolatex particles (R2 = 0.05). These results suggest that both the blood circulation time and the extent of hydration of the nanoparticles play an important role in the tumor uptake of nanoparticles. Prolonged blood circulation of these NIRF nanoparticles allowed clear visualization of tumors with γ-scintigraphy and optical imaging after intravenous administration. A better understanding with regard to how the characteristics of nanoparticles influence their in vivo behavior is an important step towards designing NIRF nanoparticles suitable for molecular imaging applications and for efficient tumor delivery.
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