Journal
ACS NANO
Volume 8, Issue 6, Pages 5852-5862Publisher
AMER CHEMICAL SOC
DOI: 10.1021/nn5008572
Keywords
ultrasmall gold nanoparticles; cancer cell nucleus; size-dependent; gene regulation; cancer therapy
Categories
Funding
- Chinese Natural Science Foundation project [81171455]
- National Natural Science Foundation of China [31225009]
- National Key Basic Research Program of China [2009CB930200, SS2014AA020708]
- Chinese Academy of Sciences (CAS) Hundred Talents Program [07165111ZX]
- CAS Knowledge Innovation Program
- State High-Tech Development Plan [2012AA020804]
- NIH/NIMHD [8 G12 MD007597]
- USAMRMC [W81XWH-10-1-0767]
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDA09030301]
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The aim of this study was to determine the size-dependent penetration ability of gold nanoparticles and the potential application of ultrasmall gold nanoparticles for intranucleus delivery and therapy. We synthesized gold nanoparticles with diameters of 2, 6, 10, and 16 nm and compared their intracellular distribution in MCF-7 breast cancer cells. Nanoparticles smaller than 10 nm (2 and 6 nm) could enter the nucleus, whereas larger ones (10 and 16 nm) were found only in the cytoplasm. We then investigated the possibility of using ultrasmall 2 nm nanoparticles as carriers for nuclear delivery of a triplex-forming oligonucleotide (TFO) that binds to the c-myc promoter. Compared to free TFO, the nanoparticle-conjugated TFO was more effective at reducing c-myc RNA and c-myc protein, which resulted in reduced cell viability. Our result demonstrated that the entry of gold nanoparticles into the cell nucleus is critically dependent on the size of the nanoparticles. We developed a strategy for regulating gene expression, by directly delivering TFOs into the nucleus using ultrasmall gold nanoparticles. More importantly, guidelines were provided to choose appropriate nanocarriers for different biomedical purposes.
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