Physicochemical signatures of nanoparticle-dependent complement activation.
Physicochemical signatures of nanoparticle-dependent complement activation.
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DOI：
10.1088/1749-4699/7/1/015003
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发表时间：
2014-03-21
期刊：
影响因子：
--
通讯作者：
Baker NA
中科院分区：
文献类型：
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作者：
Thomas DG;Chikkagoudar S;Heredia-Langer A;Tardiff MF;Xu Z;Hourcade DE;Pham CT;Lanza GM;Weinberger KQ;Baker NA
纳米颗粒是潜在的强大治疗工具，能够靶向药物有效负载和成像剂。然而，一些纳米颗粒可以激活补体（先天免疫系统的一个分支），并引起不良副作用。最近，我们采用体外溶血测定来测量不同尺寸、表面电荷和表面化学性质的全氟化碳纳米颗粒的血清补体活性，并使用称为残留溶血活性（RHA）的指标来量化纳米颗粒依赖性补体活性。在目前的工作中，我们使用决策树学习算法来根据溶血测定研究生成的数据导出估计纳米颗粒依赖性补体反应的规则。我们的结果表明，纳米颗粒的物理化学性质，即尺寸、多分散指数、zeta 电位和纳米颗粒活性表面配体的摩尔百分比，可以作为决策树建模框架中预测纳米颗粒依赖性补体激活的良好描述符。
Nanoparticles are potentially powerful therapeutic tools that have the capacity to target drug payloads and imaging agents. However, some nanoparticles can activate complement, a branch of the innate immune system, and cause adverse side-effects. Recently, we employed an in vitro hemolysis assay to measure the serum complement activity of perfluorocarbon nanoparticles that differed by size, surface charge, and surface chemistry, quantifying the nanoparticle-dependent complement activity using a metric called Residual Hemolytic Activity (RHA). In the present work, we have used a decision tree learning algorithm to derive the rules for estimating nanoparticle-dependent complement response based on the data generated from the hemolytic assay studies. Our results indicate that physicochemical properties of nanoparticles, namely, size, polydispersity index, zeta potential, and mole percentage of the active surface ligand of a nanoparticle, can serve as good descriptors for prediction of nanoparticle-dependent complement activation in the decision tree modeling framework.