Recognition-mediated activation of therapeutic gold nanoparticles inside living cells.

Recognition-mediated activation of therapeutic gold nanoparticles inside living cells.
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DOI:
10.1038/nchem.858
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发表时间:
2010-11
期刊:
影响因子:
21.8
通讯作者:
Rotello, Vincent M.
Rotello, Vincent M.
中科院分区:
化学1区
文献类型:
--
作者:
Kim, Chaekyu;Agasti, Sarit S.;Zhu, Zhengjiang;Isaacs, Lyle;Rotello, Vincent M.

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超分子化学提供了一种通用的工具,用于将分子系统组织成功能结构,并通过互补组分之间的可逆缔合来驱动这些组装体用于应用。由于细胞环境的化学复杂性和缺乏传统超分子相互作用的选择性,这种方法在生命系统中的应用代表了一个重大的挑战。本文中,我们提出了一种以二氨基己烷封端的金纳米颗粒(AuNP-NH 2)和互补葫芦[7]脲(CB[7])为特征的主-客体体系。在该系统中,CB[7]在颗粒表面上的穿线通过将颗粒隔离在内体中降低AuNP-NH 2的细胞毒性。然后通过施用1-金刚烷胺(ADA),从纳米颗粒表面去除CB[7]并触发AuNP-NH 2的内体释放和伴随的原位细胞毒性来实现AuNP-NH 2的治疗效果的细胞内触发。这种细胞内激活的超分子策略为潜在的治疗应用提供了新的工具。
Supramolecular chemistry provides a versatile tool for the organization of molecular systems into functional structures and the actuation of these assemblies for applications through the reversible association between complementary components. Application of this methodology in living systems represents a significant challenge due to the chemical complexity of cellular environments and lack of selectivity of conventional supramolecular interactions. Herein, we present a host-guest system featuring diaminohexane-terminated gold nanoparticles (AuNP-NH2) and complementary cucurbit[7]uril (CB[7]). In this system, threading of CB[7] on the particle surface reduces the cytotoxicity of AuNP-NH2 through sequestration of the particle in endosomes. Intracellular triggering of the therapeutic effect of AuNP-NH2 was then achieved via the administration of 1-adamantylamine (ADA), removing CB[7] from the nanoparticle surface and triggering the endosomal release and concomitant in situ cytotoxicity of AuNP-NH2. This supramolecular strategy for intracellular activation provides a new tool for potential therapeutic applications.
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