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CaCO₃/CaIP₆ composite nanoparticles effectively deliver AKT1 small interfering RNA to inhibit human breast cancer growth.

Zhou H, Wei J, Dai Q, Wang L, Luo J, Cheang T, Wang S - Int J Nanomedicine (2015)

Bottom Line: ACC/CaIP6 nanoparticles effectively transfected cells with little or no toxicity.AKT1 knockdown by ACC/CaIP6/siAKT1 inhibited cell cycle progression and promoted apoptosis of MCF-7 cells.ACC/CaIP6 nanoparticles are a safe and efficient method of delivering siRNA for gene therapy in breast cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurological Intensive Care Unit, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China.

ABSTRACT

Background: Small interfering RNA (siRNA)-mediated gene therapy is a promising strategy to temporarily inhibit the expression of genes involved in development of breast cancer. The lack of a safe and efficient gene delivery system has become a major hurdle for siRNA-mediated gene therapy in breast cancer. Our previous studies have demonstrated that inorganic amorphous calcium carbonate (ACC) hybrid nanospheres functionalized with CaIP6 (ACC/CaIP6) nanoparticles are an efficient nucleic acid delivery tool. The present study aimed to evaluate the safety and efficiency of ACC/CaIP6 in delivering siRNA targeting AKT1 (siAKT1) for the treatment of breast cancer.

Methods: The cytotoxicity of the ACC/CaIP6 nanoparticles was evaluated using a tetrazolium assay. The transfection efficiency and intracellular distribution of ACC/siAKT1 were analyzed by flow cytometry and confocal laser scanning microscopy, respectively. A series of in vitro and in vivo assays was performed to evaluate the effects of ACC/CaIP6/siAKT1 on growth of breast cancer cells.

Results: ACC/CaIP6 nanoparticles effectively transfected cells with little or no toxicity. AKT1 knockdown by ACC/CaIP6/siAKT1 inhibited cell cycle progression and promoted apoptosis of MCF-7 cells. Intratumoral injection of ACC/CaIP6/siAKT1 significantly suppressed the growth of breast cancer in mice.

Conclusion: ACC/CaIP6 nanoparticles are a safe and efficient method of delivering siRNA for gene therapy in breast cancer.

No MeSH data available.


Related in: MedlinePlus

Intracellular siAKT1 distribution in MCF-7 cells.Notes: FAM-siAKT1 were labeled with fluorescein (green). Cell nuclei were stained with DAPI (blue).Abbreviations: FAM-siAKT1, fluorescein-labeled AKT1-specific small interfering RNA; DAPI, 4′,6-diamidino-2-phenylindole.
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f4-ijn-10-4255: Intracellular siAKT1 distribution in MCF-7 cells.Notes: FAM-siAKT1 were labeled with fluorescein (green). Cell nuclei were stained with DAPI (blue).Abbreviations: FAM-siAKT1, fluorescein-labeled AKT1-specific small interfering RNA; DAPI, 4′,6-diamidino-2-phenylindole.

Mentions: MCF-7 cells were cultured on glass coverslips and incubated with ACC/CaIP6/FAM-siAKT1 complexes to determine whether the nanoparticle complexes could enter the cells. The intracellular distribution of FAM-siAKT1 was observed using confocal laser scanning microscopy. ACC/CaIP6/FAM-siAKT1 complexes (green) were first observed in the MCF-7 cells 1 hour after incubation (Figure 4). At 1 hour, the complexes were mainly distributed at the cell membrane. After 2 hours of incubation, the complexes were distributed in the cytoplasm and along the periphery of the nuclei. FAM-siRNA fluorescence intensity varied considerably, but gradually increased over 8 hours.


CaCO₃/CaIP₆ composite nanoparticles effectively deliver AKT1 small interfering RNA to inhibit human breast cancer growth.

Zhou H, Wei J, Dai Q, Wang L, Luo J, Cheang T, Wang S - Int J Nanomedicine (2015)

Intracellular siAKT1 distribution in MCF-7 cells.Notes: FAM-siAKT1 were labeled with fluorescein (green). Cell nuclei were stained with DAPI (blue).Abbreviations: FAM-siAKT1, fluorescein-labeled AKT1-specific small interfering RNA; DAPI, 4′,6-diamidino-2-phenylindole.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4494612&req=5

f4-ijn-10-4255: Intracellular siAKT1 distribution in MCF-7 cells.Notes: FAM-siAKT1 were labeled with fluorescein (green). Cell nuclei were stained with DAPI (blue).Abbreviations: FAM-siAKT1, fluorescein-labeled AKT1-specific small interfering RNA; DAPI, 4′,6-diamidino-2-phenylindole.
Mentions: MCF-7 cells were cultured on glass coverslips and incubated with ACC/CaIP6/FAM-siAKT1 complexes to determine whether the nanoparticle complexes could enter the cells. The intracellular distribution of FAM-siAKT1 was observed using confocal laser scanning microscopy. ACC/CaIP6/FAM-siAKT1 complexes (green) were first observed in the MCF-7 cells 1 hour after incubation (Figure 4). At 1 hour, the complexes were mainly distributed at the cell membrane. After 2 hours of incubation, the complexes were distributed in the cytoplasm and along the periphery of the nuclei. FAM-siRNA fluorescence intensity varied considerably, but gradually increased over 8 hours.

Bottom Line: ACC/CaIP6 nanoparticles effectively transfected cells with little or no toxicity.AKT1 knockdown by ACC/CaIP6/siAKT1 inhibited cell cycle progression and promoted apoptosis of MCF-7 cells.ACC/CaIP6 nanoparticles are a safe and efficient method of delivering siRNA for gene therapy in breast cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurological Intensive Care Unit, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China.

ABSTRACT

Background: Small interfering RNA (siRNA)-mediated gene therapy is a promising strategy to temporarily inhibit the expression of genes involved in development of breast cancer. The lack of a safe and efficient gene delivery system has become a major hurdle for siRNA-mediated gene therapy in breast cancer. Our previous studies have demonstrated that inorganic amorphous calcium carbonate (ACC) hybrid nanospheres functionalized with CaIP6 (ACC/CaIP6) nanoparticles are an efficient nucleic acid delivery tool. The present study aimed to evaluate the safety and efficiency of ACC/CaIP6 in delivering siRNA targeting AKT1 (siAKT1) for the treatment of breast cancer.

Methods: The cytotoxicity of the ACC/CaIP6 nanoparticles was evaluated using a tetrazolium assay. The transfection efficiency and intracellular distribution of ACC/siAKT1 were analyzed by flow cytometry and confocal laser scanning microscopy, respectively. A series of in vitro and in vivo assays was performed to evaluate the effects of ACC/CaIP6/siAKT1 on growth of breast cancer cells.

Results: ACC/CaIP6 nanoparticles effectively transfected cells with little or no toxicity. AKT1 knockdown by ACC/CaIP6/siAKT1 inhibited cell cycle progression and promoted apoptosis of MCF-7 cells. Intratumoral injection of ACC/CaIP6/siAKT1 significantly suppressed the growth of breast cancer in mice.

Conclusion: ACC/CaIP6 nanoparticles are a safe and efficient method of delivering siRNA for gene therapy in breast cancer.

No MeSH data available.


Related in: MedlinePlus