Rapid pharmacokinetic and biodistribution studies using cholorotoxin-conjugated iron oxide nanoparticles: a novel non-radioactive method.
Rapid pharmacokinetic and biodistribution studies using cholorotoxin-conjugated iron oxide nanoparticles: a novel non-radioactive method.
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DOI：
10.1371/journal.pone.0009536
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发表时间：
2010-03-04
期刊：
影响因子：
3.7
通讯作者：
Olson JM
中科院分区：
文献类型：
--
作者：
Lee MJ;Veiseh O;Bhattarai N;Sun C;Hansen SJ;Ditzler S;Knoblaugh S;Lee D;Ellenbogen R;Zhang M;Olson JM
纳米技术的最新进展导致了生物相容性纳米颗粒的发展，用于体内分子成像和靶向治疗。许多纳米颗粒具有不期望的组织分布或不可接受的低血清半衰期。药代动力学（PK）和生物分布研究可以帮助在纳米颗粒开发的早期确定颗粒大小，涂层或其他特征。不幸的是，这些研究很少能及时完成，因为许多纳米技术实验室缺乏资源和专业知识来合成放射性纳米粒子并在小鼠中进行评估。为了解决这个问题，我们开发了一种经济的、无放射性的方法来评估纳米颗粒在小鼠中的血清半衰期和组织分布。利用氯毒素作为靶向分子的用壳聚糖和聚乙二醇涂覆的氧化铁纳米颗粒具有7-8小时的血清半衰期，并且颗粒在生理流体和体内保持稳定延长的时间段。纳米颗粒优先分布到脾脏和肝脏，可能是由于网状内皮细胞摄取。其他器官的纳米颗粒水平非常低，这是未来大多数癌症成像的理想选择。没有急性毒性归因于纳米颗粒。我们在这里报告了一个简单的近红外荧光为基础的方法来评估纳米颗粒的PK特性，以便将药代动力学数据整合到早期的纳米颗粒的设计和合成。测试的纳米颗粒表现出优异的性能，用于未来的临床成像策略，并可能适用于靶向治疗。
Recent advances in nanotechnology have led to the development of biocompatible nanoparticles for in vivo molecular imaging and targeted therapy. Many nanoparticles have undesirable tissue distribution or unacceptably low serum half-lives. Pharmacokinetic (PK) and biodistribution studies can help inform decisions determining particle size, coatings, or other features early in nanoparticle development. Unfortunately, these studies are rarely done in a timely fashion because many nanotechnology labs lack the resources and expertise to synthesize radioactive nanoparticles and evaluate them in mice. To address this problem, we developed an economical, radioactivity-free method for assessing serum half-life and tissue distribution of nanoparticles in mice. Iron oxide nanoparticles coated with chitosan and polyethylene glycol that utilize chlorotoxin as a targeting molecule have a serum half-life of 7–8 hours and the particles remain stable for extended periods of time in physiologic fluids and in vivo. Nanoparticles preferentially distribute to spleen and liver, presumably due to reticuloendothelial uptake. Other organs have very low levels of nanoparticles, which is ideal for imaging most cancers in the future. No acute toxicity was attributed to the nanoparticles. We report here a simple near-infrared fluorescence based methodology to assess PK properties of nanoparticles in order to integrate pharmacokinetic data into early nanoparticle design and synthesis. The nanoparticles tested demonstrate properties that are excellent for future clinical imaging strategies and potentially suitable for targeted therapy.
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影响因子：
4.9
作者：
Alexis F;Pridgen E;Molnar LK;Farokhzad OC
通讯作者：
Farokhzad OC
影响因子：
11.2
作者：
Veiseh O;Sun C;Fang C;Bhattarai N;Gunn J;Kievit F;Du K;Pullar B;Lee D;Ellenbogen RG;Olson J;Zhang M
通讯作者：
Zhang M
影响因子：
13.3
作者：
Fang, Chen;Bhattarai, Narayan;Sun, Conroy;Zhang, Miqin
通讯作者：
Zhang, Miqin
影响因子：
4.5
作者：
Kaul, G;Amiji, M
通讯作者：
Amiji, M
影响因子：
14
作者：
Sheng, Yan;Liu, Changsheng;Xu, Feng
通讯作者：
Xu, Feng