Abstract
Abstract Nanoparticles (NPs) are ideal vectors to deliver analytic probes or therapeutic agents into cells and subcellular compartments. Among many nanomaterials, gold NPs is widely used as a model platform for biomedical research because of their favorable physical and chemical properties. Thus, gold NPs has been employed for various applications, especially in medicine. Through surface modification of gold NPs with functional bio-macromolecules (i.e., peptides, nucleic acids and antibodies) may improve the ability of imaging, clinical diagnostics and therapeutics. Cellular uptake of gold NPs is highly dependent on their size, shape, and surface properties. For targeted therapy, the common strategy for specific cells or cellular compartments delivery is to modify NPs with peptides or lignads. The outcome is highly dependent on the peptide sequence and cell types. Therefore, we treated CaSKi, HeLa and SiHa cervical cancer cells with different peptide-modified gold NPs for 24 hours and determined the cellular localization of the NPs from laser confocal microscopy equipped with DIC channel. We found that gold NPs modified with the nuclear localization signal (NLS) peptide from SV40 virus (GNP-PEG/SV40) accumulated around the cytoplasmic side of nuclear membrane (perinuclear accumulation) in CaSKi and HeLa carcinoma cells and translocate into nucleus in SiHa squamous cells. For adenovirus (ADV) peptide modified NPs (GNP-PEG/ADV), nuclear localization was observed in all cervical cancer cells. We then performed cell survival test (MTT assay) for various time intervals (24 to 96 hours) to identify the relationship between NPs’ distribution and cellular response. The particles exhibited perinuclear and nuclear accumulation decreased cell survival greater than cell and particles control (GNP-PEG) did. For perinuclear accumulation in HeLa cells, through annexin V/PI stain, there was no increase in apoptosis after long-term treatment with GNP-PEG/SV40 particles, but a significant increase in LC3-II expression in the GNP-PEG/SV40-treated group, suggesting activation of autophagy. On the contrary, an apoptotic cell population was found in nuclear accumulated SiHa cells. These findings suggest that different cellular distribution of NPs may link with specific death pathways. In conclusion, this study may have implications in the development of new therapeutic modality for specific cancer cells or prevention of long-term toxicities from treatment with different peptide modified NPs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 375. doi:10.1158/1538-7445.AM2011-375
Published Version
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