Direct Observation of Nanoparticle-Cancer Cell Nucleus Interactions

被引:254
作者
Dam, Duncan Hieu M. [1 ]
Lee, Jung Heon [1 ,4 ]
Sisco, Patrick N. [1 ]
Co, Dick T. [1 ]
Zhang, Ming [3 ]
Wasielewski, Michael R. [1 ]
Odom, Teri W. [1 ,2 ]
机构
[1] Northwestern Univ, Dept Chem, Evanston, IL 60208 USA
[2] Northwestern Univ, Dept Mat Sci & Engn, Evanston, IL 60208 USA
[3] Northwestern Univ, Dept Mol Pharmacol & Biol Chem, Chicago, IL 60611 USA
[4] Sungkyunkwan Univ SKKU, Sch Adv Mat Sci & Engn, Suwon 400746, South Korea
基金
美国国家科学基金会; 美国国家卫生研究院;
关键词
gold nanoparticles; aptamers; nucleolin; drug delivery; light-triggered release; nanoparticle-nucleus interactions; GOLD NANOPARTICLES; DNA; NUCLEOLIN; RELEASE; AS1411; OLIGONUCLEOTIDES; RECEPTORS; DISCOVERY; DELIVERY; CYCLE;
D O I
10.1021/nn300296p
中图分类号
O6 [化学];
学科分类号
070301 [无机化学];
摘要
We report the direct visualization of interactions between drug-loaded nanoparticles and the cancer cell nucleus. Nanoconstructs composed of nucleolin-specific aptamers and gold nanostars were actively transported to the nucleus and induced major changes to the nuclear phenotype via nuclear envelope invaginations near the site of the construct. The number of local deformations could be increased by ultrafast, light-triggered release of the aptamers from the surface of the gold nanostars. Cancer cells with more nuclear envelope folding showed increased caspase 3 and 7 activity (apoptosis) as well as decreased cell viability. This newly revealed correlation between drug-induced changes in nuclear phenotype and increased therapeutic efficacy could provide new insight for nuclear-targeted cancer therapy.
引用
收藏
页码:3318 / 3326
页数:9
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