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Grafting aptamers onto gold nanostars increases in vitro efficacy in a wide range of cancer cell types.

ABSTRACT: We report the design of a nanoconstruct that can function as a cell-type independent agent by targeting the ubiquitous protein nucleolin. Gold nanostars (AuNS) loaded with high densities of nucleolin-specific DNA aptamer AS1411 (Apt-AuNS) produced anticancer effects in a panel of 12 cancer lines containing four representative subcategories. We found that the nanoconstructs could be internalized by cancer cells and trafficked to perinuclear regions. Apt-AuNS resulted in downregulation of antiapoptotic Bcl-2 mRNA expression by ca. 200% compared to cells without the nanoconstructs. The caspase 3/7 activity (apoptosis) and cell death in cancer cells treated with Apt-AuNS increased by 1.5 times and by ca. 17%, respectively, compared to cells treated with free AS1411 at over 10 times the concentration. Moreover, light-triggered release of aptamer from the AuNS further enhanced the in vitro efficacy of the nanoconstructs in the cancer line panel with a 2-fold increase in caspase activity and a 40% decrease in cell viability compared to treatment with Apt-AuNS only. In contrast, treatments of the nanoconstructs with or without light-triggered release on a panel of normal cell lines had no adverse effects.

SUBMITTER: Dam DH

PROVIDER: S-EPMC3974612 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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Grafting aptamers onto gold nanostars increases in vitro efficacy in a wide range of cancer cell types.

Dam Duncan Hieu M DH Culver Kayla S B KS Odom Teri W TW

Molecular pharmaceutics 20140121 2

We report the design of a nanoconstruct that can function as a cell-type independent agent by targeting the ubiquitous protein nucleolin. Gold nanostars (AuNS) loaded with high densities of nucleolin-specific DNA aptamer AS1411 (Apt-AuNS) produced anticancer effects in a panel of 12 cancer lines containing four representative subcategories. We found that the nanoconstructs could be internalized by cancer cells and trafficked to perinuclear regions. Apt-AuNS resulted in downregulation of antiapop ...[more]

PMID: 24422969

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Project description:Low temperature is a major environmental factor that severely impairs plant growth and productivity. Watermelon (Citrullus lanatus) is a chilling-sensitive crop. Grafting of watermelon onto pumpkin rootstock is an effective technique to increase the chilling tolerance of watermelon when exposure to short-time chilling stress. However, the mechanism by which pumpkin rootstock increases chilling tolerance remains poorly understood. Under 10°C/5°C (day/night) chilling stress treatment, pumpkin-grafted watermelon seedlings showed higher chilling tolerance than self-grafted watermelon plants with significantly reduced lipid peroxidation and chilling injury (CI) index. Physiological analysis revealed that pumpkin rootstock grafting led to the notable accumulation of putrescine in watermelon seedlings under chilling conditions. Pre-treat foliar with 1 mM D-arginine (inhibitor of arginine decarboxylase, ADC) increased the electrolyte leakage (EL) of pumpkin-grafted watermelon leaves under chilling stress. This result can be ascribed to the decrease in transcript levels of ADC, ornithine decarboxylase, spermidine synthase, and polyamine oxidase genes involved in the synthesis and metabolism of polyamines. Transcriptome analysis showed that pumpkin rootstock improved chilling tolerance in watermelon seedlings by regulating differential gene expression under chilling stress. Pumpkin-grafted seedling reduced the number and expression level of differential genes in watermelon scion under chilling stress. It specifically increased the up-regulated expression of ADC (Cla97C11G210580), a key gene in the polyamine metabolism pathway, and ultimately promoted the accumulation of putrescine. In conclusion, pumpkin rootstock grafting increased the chilling tolerance of watermelon through transcription adjustments, up regulating the expression level of ADC, and promoting the synthesis of putrescine, which ultimately improved the chilling tolerance of pumpkin-grafted watermelon plants.

Dataset Information

Grafting aptamers onto gold nanostars increases in vitro efficacy in a wide range of cancer cell types.

Publications

Grafting aptamers onto gold nanostars increases in vitro efficacy in a wide range of cancer cell types.

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