Grafting Aptamers onto Gold Nanostars Increases <i>in Vitro</i> Efficacy in a Wide Range of Cancer Cell Types

Dam, Duncan Hieu M.; Culver, Kayla S. B.; Odom, Teri W.

doi:10.1021/mp4005657

Cited by 85 publications

(91 citation statements)

References 36 publications

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“…These particles were taken up by pancreatic cancer cells and fibrosarcoma cells at a faster rate, resulting in increased death of cancer cells. Interestingly, treatments with these nanoconstructs had no adverse effects on normal cell lines [115].…”

Section: Gold Nanostarsmentioning

confidence: 98%

How toxic are gold nanoparticles? The state-of-the-art

et al. 2015

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With the growing interest in the applications of gold nanoparticles in biotechnology and their physiological effects, possible toxicity of gold nanoparticles is becoming an increasingly important issue. A large number of studies carried out over the past few years under a variety of experimental conditions and following different protocols have produced conflicting results, leading to divergent views about the actual safety of gold nanoparticles in human applications.This work is intended to provide an overview of the most recent experimental results and thereby summarize current state-of-the-art. Rather than presenting a comprehensive review of the available literature in this field, which would be impractically broad, we have selected representative examples of both in vivo and in vitro studies, which clearly demonstrate the need for urgent and rigorous standardization of experimental protocols. Despite their significant potential, the safety of gold nanoparticles is highly controversial at this time, and important concerns have been raised that need to be properly addressed. Factors such as shape, size, surface charge, coating, and surface functionalization are expected to influence the interactions of particles with biological systems to a different extent, resulting in different outcomes and influencing the potential of gold nanoparticles for biomedical applications.Moreover, despite continuous attempts to establish a correlation between structure of the particles and their interactions with biological systems, we are still far from elucidating the toxicological profile of gold nanoparticles in an indisputable manner. This review is intended to contribute towards this goal, offering a number of suggestions on how to achieve the systematization of data on the most relevant physico-chemical parameters, which govern and control the toxicity of gold nanoparticles at cellular and whole-organism levels.

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Section: Gold Nanostarsmentioning

confidence: 98%

How toxic are gold nanoparticles? The state-of-the-art

et al. 2015

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“…10, 39 Interactions between the nanoconstruct and the nucleus resulted in severe deformation of the nuclear envelope, double-stranded DNA breaks in the nucleus, and ultimately, apoptosis of cancer cells. 9, 10 The treatment of nanoconstructs in tandem with NIR, light-triggered release of AS1411 at the localized surface plasmon (LSP) resonance of AuNS increased the percentage of cancer cell death by 50% compared to treatment with only the nanoconstruct. 9 Importantly, NCL is one of few ubiquitous proteins that have been discovered on the surface of diverse cancer cell types.…”

Section: Introductionmentioning

confidence: 99%

Biodistribution and in vivo toxicity of aptamer-loaded gold nanostars

Dam

Culver

Kandela

et al. 2015

Nanomedicine: Nanotechnology, Biology and Medicine

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This paper reports an in vivo evaluation of toxicology and biodistribution of a highly anisotropic Au nanoconstruct composed of a gold nanostar (AuNS) core and a ligand shell of a G-quadruplex DNA aptamer AS1411 (Apt) supporting both targeting and therapy capabilities. We examined the toxicity of the nanoconstructs (Apt-AuNS) at four different injected concentrations; at the highest dose tested (48 mg/kg), maximal tolerated dose was not reached. Complete assessment of clinical pathology showed no apparent signs of acute toxicity. Interestingly, the nanoconstructs circulated longer in female rats compared to male rats. In two different tumor models, the biodistribution of Apt-AuNS, especially tumor accumulation, was different. Accumulation of Apt-AuNS was 5 times higher in invasive breast cancer tumors compared to fibrosarcoma tumors. These results provide insight on identifying a tumor model and nanoconstruct for in vivo studies, especially when an in vitro therapeutic response is observed in multiple cancer cell lines.

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“…In addition, the anticancer effect was drastically potentiated with light-triggered release of AS1411 from gold nanostars owed to a high localized concentration of AS1411detached from the NPs. Finally, AS1411 conjugated to NPs showed higher anticancer potential compared to the free AS1411 exceeding 10 times the concentration, with a 17% higher average cell death, emphasizing the importance of NPs as a platform to insure stability and high local concentrations of the drug [75]. Using high resolution TEM, the same group reported deformation of the nuclear envelope that correlated in 80% with the location of AS1411-gold nanoconstruct near the nucleus of HeLa cells.…”

Section: As1411 Aptamer Conjugated Nps Targeting Nclmentioning

confidence: 96%

Nanoparticles Functionalized with Ligands of Cell Surface Nucleolin for Cancer Therapy and Diagnosis

Destouches¹

2015

J Nanomed Nanotechnol

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Conventional cancer chemotherapies are often limited by their non-targeted nature and their inadequate delivery to the tumor affecting the normal tissues and leading to toxic adverse effects. In order to improve the anticancer efficacy and safety of these drugs, as well as the diagnosis capacity of imaging agents, nanoparticles drug delivery system has been developed combining ligands enabling tumor targeting at a cellular level and drug carrier capacity. Nucleolin (NCL) is a multifunctional protein that could shuttle from nucleolus to nucleoplasm, cytoplasm and cell surface. This ribonucleo protein over expressed at the cell surface of cancer cells is involved in many cancer processes supporting tumorigenesis such as cell proliferation and apoptosis. Additionally, NCL expression is enhanced in angiogenic vessels, enabling multi-targeting strategies toward the tumor microenvironment. In this context, several compounds targeting NCL, such as the aptamer AS1411, the peptide F3 and the multivalent pseudopeptide N6L, have been developed and investigated for cancer therapy. Due to their cancer cell targeting capacities, these compounds have been evaluated to mediate highly specific and effective nanoparticles for drug delivery to the tumor. In this report, we present a review of literature focusing on drug-loaded nanoparticles conjugated with these nucleolin ligands, strikingly emphasizing the success of such a strategy.

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Grafting Aptamers onto Gold Nanostars Increases in Vitro Efficacy in a Wide Range of Cancer Cell Types

Cited by 85 publications

References 36 publications

How toxic are gold nanoparticles? The state-of-the-art

How toxic are gold nanoparticles? The state-of-the-art

Biodistribution and in vivo toxicity of aptamer-loaded gold nanostars

Nanoparticles Functionalized with Ligands of Cell Surface Nucleolin for Cancer Therapy and Diagnosis

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