Ultrasmall gold nanoparticles as carriers for nucleus-based gene therapy due to size-dependent nuclear entry.
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.
Chinese Academy of Sciences (CAS) Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, No.11, First North Road, Zhongguancun, Beijing, China 100190.
Shuaidong
S
Huo
Shubin
S
Jin
Xiaowei
X
Ma
Xiangdong
X
Xue
Keni
K
Yang
Anil
A
Kumar
Paul C
PC
Wang
Jinchao
J
Zhang
Zhongbo
Z
Hu
Xing-Jie
XJ
Liang
D001943:Breast Neoplasms / Q000628:therapy*; D002467:Cell Nucleus / Q000378:metabolism*; D002470:Cell Survival; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006046:Gold / Q000737:chemistry*; D006801:Humans; D061986:MCF-7 Cells; D053768:Metal Nanoparticles / Q000737:chemistry*; D036103:Nanotechnology / Q000379:methods*; D009841:Oligonucleotides / Q000737:chemistry; D011401:Promoter Regions, Genetic; D016271:Proto-Oncogene Proteins c-myc / Q000737:chemistry; D012313:RNA / Q000737:chemistry
D009841:Oligonucleotides; D016271:Proto-Oncogene Proteins c-myc; D012313:RNA; D006046:Gold