Pharmacokinetics, clearance, and biosafety of polyethylene glycol-coated hollow gold nanospheres.
Pharmacokinetics, clearance, and biosafety of polyethylene glycol-coated hollow gold nanospheres.
复制标题
聚乙二醇包被的空心金纳米球的药代动力学、清除率和生物安全性
DOI：
10.1186/1743-8977-11-26
复制
发表时间：
2014-05-30
影响因子：
10
通讯作者：
Li C
中科院分区：
文献类型：
--
作者：
You J;Zhou J;Zhou M;Liu Y;Robertson JD;Liang D;Van Pelt C;Li C
目的金纳米颗粒作为一种潜在的治疗药物引起了人们的极大兴趣。然而，文献中对金纳米颗粒的长期消除和全身毒性知之甚少。空心金纳米球（HAuNS）是一类光热导电剂，在光声成像、光热消融治疗和药物输送等方面具有广阔的应用前景。明确haun的生物安全性是其进一步应用的必要条件。方法研究聚乙二醇（PEG）包被HAuNS （PEG-HAuNS，平均直径63 nm）的体外细胞毒性、补体活化和血小板聚集，以及其在小鼠体内的药代动力学、生物分布、器官消除、血液学、临床化学、急性毒性和慢性毒性。结果speg - hauns未诱导可检测到的补体系统激活，也未诱导可检测到的血小板聚集。PEG-HAuNS在小鼠血液中的半衰期为8.19±1.4小时。PEG-HAuNS在光热消融治疗中的单次有效剂量为12.5 mg/kg。PEG-HAuNS在2周内每天静脉注射10次，每次注射12.5 mg/kg（累积剂量：125 mg/kg），无不良反应。对小鼠肌肉、肝脏、脾脏和肾脏的定量分析显示，从第一次静脉注射后的第14天到第90天，Au水平分别下降了45.2%、28.6%、41.7%和40.8%，表明PEG-HAuNS在这些器官中被缓慢清除。结论PEG-HAuNS是一种很有前途的光热导剂。
ObjectiveGold nanoparticles have attracted enormous interest as potential theranostic agents. However, little is known about the long-term elimination and systemic toxicity of gold nanoparticles in the literature. Hollow gold nanospheres (HAuNS) is a class of photothermal conducting agent that have shown promises in photoacoustic imaging, photothermal ablation therapy, and drug delivery. It’s very necessary to make clear the biosafety of HAuNS for its further application.MethodsWe investigated the cytotoxicity, complement activation, and platelet aggregation of polyethylene glycol (PEG)-coated HAuNS (PEG-HAuNS, average diameter of 63 nm)in vitroand their pharmacokinetics, biodistribution, organ elimination, hematology, clinical chemistry, acute toxicity, and chronic toxicity in mice.ResultsPEG-HAuNS did not induce detectable activation of the complement system and did not induce detectable platelet aggregation. The blood half-life of PEG-HAuNS in mice was 8.19 ± 1.4 hr. The single effective dose of PEG-HAuNS in photothermal ablation therapy was determined to be 12.5 mg/kg. PEG-HAuNS caused no adverse effects after 10 daily intravenous injections over a 2-week period at a dose of 12.5 mg/kg per injection (accumulated dose: 125 mg/kg). Quantitative analysis of the muscle, liver, spleen, and kidney revealed that the levels of Au decreased 45.2%, 28.6%, 41.7%, and 40.8%, respectively, from day 14 to day 90 after the first intravenous injection, indicating that PEG-HAuNS was slowly cleared from these organs in mice.ConclusionOur data support the use of PEG-HAuNS as a promising photothermal conducting agent.
登录
查看更多内容
影响因子：
17.1
作者：
Nusz, Greg J.;Curry, Adam C.;Marinakos, Stella M.;Wax, Adam;Chilkoti, Ashutosh
通讯作者：
Chilkoti, Ashutosh
影响因子：
15
作者：
Brown, Sarah D.;Nativo, Paola;Smith, Jo-Ann;Stirling, David;Edwards, Paul R.;Venugopal, Balaji;Flint, David J.;Plumb, Jane A.;Graham, Duncan;Wheate, Nial J.
通讯作者：
Wheate, Nial J.
影响因子：
11.2
作者：
Lu W;Zhang G;Zhang R;Flores LG 2nd;Huang Q;Gelovani JG;Li C
通讯作者：
Li C
影响因子：
4.5
作者：
Gurr, JR;Wang, ASS;Jan, KY
通讯作者：
Jan, KY
影响因子：
12.6
作者：
Lee, Sangyeop;Chon, Hyangah;Oh, Chil Hwan
通讯作者：
Oh, Chil Hwan