Ligand-clustered "patchy" nanoparticles for modulated cellular uptake and in vivo tumor targeting.
Ligand-clustered "patchy" nanoparticles for modulated cellular uptake and in vivo tumor targeting.
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DOI：
10.1002/anie.201003445
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发表时间：
2010-09-24
影响因子：
16.6
通讯作者：
Hammond, Paula T.
中科院分区：
文献类型：
--
作者：
Poon, Zhiyong;Chen, Shujun;Engler, Amanda C.;Lee, Hyung-il;Atas, Evrim;von Maltzahn, Geoffrey;Bhatia, Sangeeta N.;Hammond, Paula T.
尽管使用多价方法来增加靶向递送的功效取得了明显的成功，但尚未清楚地了解多个配体如何共同作用以影响纳米颗粒细胞靶向剂的摄取。尽管当大量存在时，多价配体可以增加与细胞的结合亲合力，但也可以想象，这些配体呈递给细胞的方式可能对摄取具有显著影响。在这里，我们使用线性树枝状聚合物结构，使我们能够在不同的空间排列的纳米粒子与不同大小的配体簇的表面图案检查这个参数。我们第一次证明了在体外和体内的细胞内摄取的叶酸介绍的明确影响。这里提出的研究结果表明，纳米颗粒表面上的配体呈递的性质可能在药物靶向中发挥重要作用;结果表明对其他靶向部分的潜在影响，并为进一步完善未来的多价靶向策略提供了框架。
Despite the evident success of using a multivalent approach to increase efficacy of targeted delivery, a clear understanding of how multiple ligands behave collectively to influence the uptake of nanoparticle cell-targeting agents has not been reached. Although when present in large quantity, multivalent ligands can increase binding avidities to cells, it is also conceivable, that the manner in which these ligands are presented to the cell may have a significant effect on uptake. Here we examine this parameter using a linear dendritic polymer construct that enabled us to pattern the surfaces of nanoparticles with variable sized ligand clusters in different spatial arrangements. We demonstrate for the first time the clear impact of folate presentation on intracellular uptake both in vitro and in vivo. The findings presented here suggest that the nature of ligand presentation on a nanoparticle surface may play an important role in drug targeting; the results suggest potential impact for other targeting moieties and provide a framework for further refinement of future multivalent targeting strategies.
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影响因子：
4.7
作者：
André, S;Kaltner, H;Gabius, HJ
通讯作者：
Gabius, HJ
影响因子：
64.8
作者：
Kitov, PI;Sadowska, JM;Bundle, DR
通讯作者：
Bundle, DR
影响因子：
10.8
作者：
Maeda, H;Wu, J;Hori, K
通讯作者：
Hori, K
影响因子：
7.3
作者：
Montet, Xavier;Funovics, Martin;Josephson, Lee
通讯作者：
Josephson, Lee
影响因子：
64.5
作者：
Lemmon MA;Schlessinger J
通讯作者：
Schlessinger J