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Pharmacokinetics and biodistribution of near-infrared fluorescence polymeric nanoparticles

机译：近红外荧光聚合物纳米粒子的药代动力学和生物分布

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摘要

There has been increased interest in the use of polymeric nanoparticles as carriers for near-infrared fluorescence (NIRF) 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 facilitate 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 versus 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 (R~2 = 0.95), but similar correlations were not found between nanogel and nanolatex particles (R~2 = 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 y-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.
机译：使用聚合物纳米颗粒作为用于癌症诊断的近红外荧光（NIRF）染料的载体的兴趣日益浓厚。但是，全身给药后纳米颗粒向肿瘤的有效递送受到各种生物屏障的限制。在这项研究中，我们调查了在荷瘤小鼠体内涂有聚乙二醇的亚纳米级聚合物纳米颗粒（直径<100 nm）的药代动力学，生物分布和肿瘤吸收。为方便我们的研究，这些颗粒用γ发射极铟111标记。我们发现两个具有相同大小（-20 nm）和化学成分但结构不同（即水凝胶与核-壳纳米胶乳）的NIRF纳米颗粒，或具有不同大小（20、30和60）的相同核-壳纳米胶乳颗粒纳米），具有不同的血液循环时间，生物分布和肿瘤吸收。有趣的是，纳米胶乳颗粒的肿瘤吸收与其血液停留时间密切相关（R〜2 = 0.95），但在纳米凝胶和纳米胶乳颗粒之间未发现相似的相关性（R〜2 = 0.05）。这些结果表明，血液循环时间和纳米颗粒的水合程度在纳米颗粒的肿瘤摄取中起重要作用。这些NIRF纳米粒子的血液循环时间延长，可以在静脉内给药后通过Y闪烁显像和光学成像清楚地观察肿瘤。关于纳米粒子的特性如何影响其体内行为的更好的理解是设计适合分子成像应用和有效肿瘤递送的NIRF纳米粒子的重要一步。

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