Effect of modifying quantum dot surface charge on airway epithelial cell uptake <i>in vitro</i>

Chau, Eric; Galloway, Justin F.; Nelson, Antoinette; Breysse, Patrick N.; Wirtz, Denis; Searson, Peter C.; Sidhaye, Venkataramana K.

doi:10.3109/17435390.2012.711862

Cited by 13 publications

(6 citation statements)

References 45 publications

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“…The comparative enhanced cytotoxicity induced by the positively charged QDs compared to the negatively charged QDs might be a function of their uptake by the cells. Indeed, studies by Chau et al 57 have demonstrated that QD charge dictates the pathway of particle traversal within a tissue, with positively charged QDs doing so intracellularly and negatively charged QDs following a paracellular mechanism. This charge-based fundamental difference in cell/QD interaction and uptake underscores the potential for differing cytotoxic mechanisms due to QD functionalization, although the authors of that study did not report cytotoxic data.…”

Section: Discussionmentioning

confidence: 99%

Functionalization-Dependent Induction of Cellular Survival Pathways by CdSe Quantum Dots in Primary Normal Human Bronchial Epithelial Cells

Nagy¹,

Hollingsworth²,

Hu³

et al. 2013

ACS Nano

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Quantum dots (QDs) are semiconductor nanocrystals exhibiting unique optical properties that can be exploited for many practical applications ranging from photovoltaics to biomedical imaging and drug delivery. A significant number of studies have alluded to the cytotoxic potential of these materials, implicating Cd-leaching as the causal factor. Here, we investigated the role of heavy metals in biological responses and the potential of CdSe-induced genotoxicity. Our results indicate that, while negatively charged QDs are relatively noncytotoxic compared to positively charged QDs, the same does not hold true for their genotoxic potential. Keeping QD core composition and size constant, 3 nm CdSe QD cores were functionalized with mercaptopropionic acid (MPA) or cysteamine (CYST), resulting in negatively or positively charged surfaces, respectively. CYST-QDs were found to induce significant cytotoxicity accompanied by DNA strand breakage. However, MPA-QDs, even in the absence of cytotoxicity and reactive oxygen species formation, also induced a high number of DNA strand breaks. QD-induced DNA damage was confirmed by identifying the presence of p53 binding protein 1 (53BP1) in the nuclei of exposed cells and subsequent diminishment of p53 from cytoplasmic cellular extracts. Further, high-throughput real-time PCR analyses revealed upregulation of DNA damage and response genes and several proinflammatory cytokine genes. Most importantly, transcriptome sequencing revealed upregulation of the metallothionein family of genes in cells exposed to MPA-QDs but not CYST-QDs. These data indicate that cytotoxic assays must be supplemented with genotoxic analyses to better understand cellular responses and the full impact of nanoparticle exposure when making recommendations with regard to risk assessment.

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Section: Discussionmentioning

confidence: 99%

Functionalization-Dependent Induction of Cellular Survival Pathways by CdSe Quantum Dots in Primary Normal Human Bronchial Epithelial Cells

Nagy¹,

Hollingsworth²,

Hu³

et al. 2013

ACS Nano

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“…The physico‐chemical binding of TiO 2 NPs with intact VE‐cadherin presupposes that TiO 2 NPs are required to navigate their way to the intercellular niche. In support of this notion, negatively charged CdSe quantum dots (QDs) were also shown to preferentially localize as early as 5 min post‐QD exposure along the cell–cell boundary of epithelial cells, whereas positively charged QDs were found to traverse through the epithelial lining via the transcellular route . Intracellularly, the binding of TiO 2 NPs to VE‐cadherin then triggers phosphorylation of VE‐cadherin at site Y658, followed by rearrangement of the cytoskeleton.…”

Section: Some New Yin and Yang Relationships Of Nms With Biological Pmentioning

confidence: 99%

Back to Basics: Exploiting the Innate Physico‐chemical Characteristics of Nanomaterials for Biomedical Applications

Tay

Setyawati

Xie

et al. 2014

Adv Funct Materials

201

182

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In nanomedicine design, emphasis is centered on the engineered impacts of the nanomaterials (NMs). However, failure to understand the unintended effects of nanomaterials on the cell biology can affect the overall performance, approval, and adoption in the clinic. Much of these unintended effects arise from unique physico-chemical properties of the NMs. This feature article discusses some of the key physico-chemical parameters of NMs and highlights how they could cause unexpected and novel biological responses, with some insights into their underlying mechanisms.

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“…Many studies seeking to understand and reduce the toxicity associated with NPs, have sought to examine them in more detail, as well as their characteristics, such as surface charge and surface pattern, which contribute to airway inflammation. 17 , 18 , 19 …”

Section: Introductionmentioning

confidence: 99%

Acute exposure to silica nanoparticles aggravate airway inflammation: different effects according to surface characteristics

et al. 2015

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Silica nanoparticles (SNPs) are widely used in many scientific and industrial fields despite the lack of proper evaluation of their potential toxicity. This study examined the effects of acute exposure to SNPs, either alone or in conjunction with ovalbumin (OVA), by studying the respiratory systems in exposed mouse models. Three types of SNPs were used: spherical SNPs (S-SNPs), mesoporous SNPs (M-SNPs), and PEGylated SNPs (P-SNPs). In the acute SNP exposure model performed, 6-week-old BALB/c female mice were intranasally inoculated with SNPs for 3 consecutive days. In the OVA/SNPs asthma model, the mice were sensitized two times via the peritoneal route with OVA. Additionally, the mice endured OVA with or without SNP challenges intranasally. Acute SNP exposure induced significant airway inflammation and airway hyper-responsiveness, particularly in the S-SNP group. In OVA/SNPs asthma models, OVA with SNP-treated group showed significant airway inflammation, more than those treated with only OVA and without SNPs. In these models, the P-SNP group induced lower levels of inflammation on airways than both the S-SNP or M-SNP groups. Interleukin (IL)-5, IL-13, IL-1β and interferon-γ levels correlated with airway inflammation in the tested models, without statistical significance. In the mouse models studied, increased airway inflammation was associated with acute SNPs exposure, whether exposed solely to SNPs or SNPs in conjunction with OVA. P-SNPs appear to be relatively safer for clinical use than S-SNPs and M-SNPs, as determined by lower observed toxicity and airway system inflammation.

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Effect of modifying quantum dot surface charge on airway epithelial cell uptake in vitro

Cited by 13 publications

References 45 publications

Functionalization-Dependent Induction of Cellular Survival Pathways by CdSe Quantum Dots in Primary Normal Human Bronchial Epithelial Cells

Functionalization-Dependent Induction of Cellular Survival Pathways by CdSe Quantum Dots in Primary Normal Human Bronchial Epithelial Cells

Back to Basics: Exploiting the Innate Physico‐chemical Characteristics of Nanomaterials for Biomedical Applications

Acute exposure to silica nanoparticles aggravate airway inflammation: different effects according to surface characteristics

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