Ultrasmall Gold Nanoparticles as Carriers for Nucleus-Based Gene Therapy Due to Size-Dependent Nuclear Entry

Abstract

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.

Gold nanoparticles for cancer theranostics — A brief update

“…42 Ultrasmall AuNPs (2 nm) as carriers for nuclear delivery of triplex-forming oligonucleotides which bind to the promoter of protooncogene c-myc for reducing the generations of c-myc RNA and c-myc protein, subsequently reduce the viability of MCF-7 breast cancer cells. 43 It also demonstrated that NPs smaller than 10 nm could enter the nucleus for intranuclear delivery and therapy, whereas larger ones were found only in the cytoplasm. Although all kinds of polymer-coated AuNPs have been developed to load more nucleotides or to deliver combinations of genetic therapies to cancer cells, 44 there are still rare examples of using AuNPs-oligonucleotides conjugates for gene theranostics in vivo.…”

Surface-enhanced Raman spectroscopy for in vivo biosensing

“…Au NPs have unique optical properties, biocompatibility and ease of functionalization that makes them particularly suitable in drug delivery, 95,99,148 controlled DNA release, [149][150][151] active tumour targeting, 52,118,144 photodynamic therapy (PDT) 94,152 and PTT. 92,98,100,153 Additionally, the use of NPs in these applications provides enhanced signals in Raman imaging and allows the processes to be monitored using SERS.…”

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“…Partially acetylated Dendrimer-entrapped gold nanoparticles (AuDENPs) delivery system was also proposed for safe gene delivery biomedical approach with improved gene transfection efficiency [19]. Recently, gold nanoparticles conjugated c-myc promoter-triplex-forming oligonucleotide (TFO) and cationic gold nanoparticles were used for improved transgene expression efficacy and intranucleus non-viral gene delivery biomedical tools [20,21].…”