Biodistribution, Clearance, and Toxicology of Polymeric Micelles Loaded with 0.9 or 5 nm Gold Nanoparticles.
Biodistribution, Clearance, and Toxicology of Polymeric Micelles Loaded with 0.9 or 5 nm Gold Nanoparticles.
复制标题
装有0.9或5 nm金纳米颗粒的聚合物胶束的生物分布，清除和毒理学。
DOI：
10.1166/jbn.2015.2142
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发表时间：
2015-10
影响因子：
2.9
通讯作者：
Tsourkas A
中科院分区：
文献类型：
--
作者：
Al Zaki A;Hui JZ;Higbee E;Tsourkas A
长循环金纳米颗粒（AuNP）作为成像剂和治疗剂引起了人们的极大兴趣。然而，它们在许多器官系统中的长期消除和长期持续存在仍然是临床转化的一个问题。为了改善长循环纳米颗粒的排泄，我们制备了约 80 nm 的可生物降解聚合物胶束，其中 0.9 nm 或 5 nm AuNP 紧密堆积在疏水核心内。与单个大金纳米粒子相比，这些载金聚合胶束 (GPM) 有望改善金的排泄，因为胶束内单个金纳米粒子的尺寸更小，表面积与体积比更大。静脉注射 GPM 后，采集器官并在注射后长达 3 个月内使用电感耦合等离子体发射光谱法 (ICP-OES) 检查金含量。虽然两种 GPM 制剂都显示出随着时间的推移显着的金清除率，但在注射后 1 天到 3 个月内，含有 0.9 nm AuNP 的胶束显示肝脏和脾脏中的金含量分别降低了 72% 和 67%，而接受 5 nm GPM 的小鼠则分别降低了 38% 和 35%。此外，粪便和尿液分析显示，注射一天后接受 0.9 nm GPM 的小鼠体内的金含量分别增加了约 7.5 倍和 100 倍。这些发现表明，如果使用小无机材料簇代替单个固体颗粒，无机纳米材料的排泄曲线可能会得到改善。
Long-circulating gold nanoparticles (AuNPs) have garnered a great deal of interest as both imaging and therapeutic agents. However, their protracted elimination and long-term persistence within many organ systems remains a concern for clinical translation. To improve the excretion of long-circulating nanoparticles, we prepared ~80 nm biodegradable polymeric micelles with 0.9 nm or 5 nm AuNPs tightly packed within the hydrophobic core. These gold-loaded polymeric micelles (GPMs) were expected to allow for improved excretion of gold, compared with single large AuNPs, owing to the smaller size and larger surface-to-volume ratio of the individual AuNPs within the micelle. Following intravenous administration of GPMs, organs were harvested and examined for gold content using inductively coupled plasma optical emission spectrometry (ICP-OES) for up to 3 months post-injection. While both GPM formulations showed significant clearance of gold over time, micelles containing 0.9 nm AuNPs showed a 72% and 67% reduction in gold content in the liver and spleen, respectively, between 1 day and 3 months post-injection, compared with a 38% and 35% reduction in mice receiving 5 nm GPMs. Furthermore, feces and urine analysis revealed approximately 7.5 and 100 times more gold, respectively, in mice that received 0.9 nm GPMs one day after injection. These findings suggest that the excretion profile of inorganic nanomaterials may be improved if clusters of small inorganic materials are used in favor of single solid particles.