Assessing bioactivity of environmental water samples filtered using nanomembrane technology and mammalian cell lines.

This project reports on the use of a novel nanomembrane filtering technology to isolate and analyze the bioactivity of microplastic (MP)-containing debris from Lake Ontario water samples. Environmental MPs are a complex mixture of polymers and sorbed chemicals that are persistent and can exhibit a wide range of toxic effects. Since human exposure to MPs is unavoidable, it is necessary to characterize their bioactivity to assess potential health risks.

Immunomodulatory effects of nanoparticles on dendritic cells in a model of allergic contact dermatitis: importance of PD-L2 expression.

Nanoparticle (NP) skin exposure is linked to an increased prevalence of allergic contact dermatitis. In our prior studies using the mouse contact hypersensitivity (CHS) model, we reported that silica 20 nm (SiO) NPs suppressed the allergic response and titanium dioxide NPs doped with manganese (mTiO) exacerbated it. In this work, we conducted in vitro experiments using bone marrow-derived dendritic cells (BMDCs) to study the combinatorial effect of the potent 2,4-dinitrofluorobenzene (DNFB) hapten sensitizer with SiO and mTiO NPs on BMDC cytotoxicity, cytokine secretion and phenotype using the B7 family ligands.

Immunomodulatory Effects of Nanoparticles on Dendritic Cells in a Model of Allergic Contact Dermatitis - Importance of PD-L2 Expression.

Nanoparticle (NP) skin exposure is linked to the increased prevalence of allergic contact dermatitis. In prior studies using the mouse contact hypersensitivity (CHS) model, we reported that silica 20 nm (Si20nm) suppressed the allergic response and TiO2 doped with manganese (mTiO2) exacerbated it. In this work, we conducted in vitro experiments using bone marrow-derived dendritic cells (BMDCs) to study the combinatorial effect of the potent 2, 4-dinitrofluorobenzene (DNFB) hapten sensitizer with Si20nm and mTiO2 NPs on BMDC cytotoxicity, cytokine secretion and phenotype using the B7 family ligands.

Slow hydrogel matrix degradation enhances salivary gland mimetic phenotype.

We recently developed a salivary gland tissue mimetic (SGm), comprised of salivary gland cells encapsulated in matrix metalloproteinase (MMP)-degradable poly(ethylene glycol) hydrogels within arrays of ∼320 µm diameter spherical cavities molded in PDMS. The SGm provides a functional and physiologically relevant platform well-suited to high-throughput drug screening for radioprotective compounds. However, the utility of the SGm would benefit from improved retention of acinar cell phenotype and function.

Optimizing Soluble Cues for Salivary Gland Tissue Mimetics Using a Design of Experiments (DoE) Approach.

The development of therapies to prevent or treat salivary gland dysfunction has been limited by a lack of functional in vitro models. Specifically, critical markers of salivary gland secretory phenotype downregulate rapidly ex vivo. Here, we utilize a salivary gland tissue chip model to conduct a design of experiments (DoE) approach to test combinations of seven soluble cues that were previously shown to maintain or improve salivary gland cell function.

Encapsulation of Primary Salivary Gland Acinar Cell Clusters and Intercalated Ducts (AIDUCs) within Matrix Metalloproteinase (MMP)-Degradable Hydrogels to Maintain Tissue Structure and Function.

Progress in the development of salivary gland regenerative strategies is limited by poor maintenance of the secretory function of salivary gland cells (SGCs) in vitro. To reduce the precipitous loss of secretory function, a modified approach to isolate intact acinar cell clusters and intercalated ducts (AIDUCs), rather than commonly used single cell suspension, is investigated. This isolation approach yields AIDUCs that maintain many of the cell-cell and cell-matrix interactions of intact glands.

Salivary Gland Tissue Engineering Approaches: State of the Art and Future Directions.

Salivary gland regeneration is important for developing treatments for radiation-induced xerostomia, Sjögren's syndrome, and other conditions that cause dry mouth. Culture conditions adopted from tissue engineering strategies have been used to recapitulate gland structure and function to study and regenerate the salivary glands. The purpose of this review is to highlight current trends in the field, with an emphasis on soluble factors that have been shown to improve secretory function in vitro.

Development of a functional salivary gland tissue chip with potential for high-content drug screening.

Radiation therapy for head and neck cancers causes salivary gland dysfunction leading to permanent xerostomia. Limited progress in the discovery of new therapeutic strategies is attributed to the lack of in vitro models that mimic salivary gland function and allow high-throughput drug screening. We address this limitation by combining engineered extracellular matrices with microbubble (MB) array technology to develop functional tissue mimetics for mouse and human salivary glands.

Silicon Nanomembrane Filtration and Imaging for the Evaluation of Microplastic Entrainment along a Municipal Water Delivery Route.

To better understand the origin of microplastics in municipal drinking water, we evaluated 50 mL water samples from different stages of the City of Rochester's drinking water production and transport route, from Hemlock Lake to the University of Rochester. We directly filtered samples using silicon nitride nanomembrane filters with precisely patterned slit-shaped pores, capturing many of the smallest particulates (<20 μm) that could be absorbed by the human body. We employed machine learning algorithms to quantify the shapes and quantity of debris at different stages of the water transport process, while automatically segregating out fibrous structures from particulate.

Morphology-dependent titanium dioxide nanoparticle-induced keratinocyte toxicity and exacerbation of allergic contact dermatitis.

Titanium dioxide (TiO) nanoparticles are commonly found in consumer products, such as sunscreens, and human dermal exposures are relatively high. Research suggests potential differences in the toxicity of anatase and rutile crystalline forms of TiO. Additionally, transition metal dopants are frequently used to enhance physicochemical properties of TiO, and the toxicity of these nanoparticles are not extensively studied.

Further studies in translatable model systems are needed to predict the impacts of human microplastic exposure.

Microplastics are a pervasive environmental contaminant that have been found in many media including water sources, soils, and foodstuff. Due to the worldwide presence and persistence of microplastic debris, human exposure is inevitable. Human exposure occurs predominantly through ingestion, although dermal and inhalation exposures are probable.

The UVR Filter Octinoxate Modulates Aryl Hydrocarbon Receptor Signaling in Keratinocytes via Inhibition of CYP1A1 and CYP1B1.

Ultraviolet radiation (UVR) is a consistent part of the environment that has both beneficial and harmful effects on human health. UVR filters in the form of commercial sunscreens have been widely used to reduce the negative health effects of UVR exposure. Despite their benefit, literature suggests that some filters can penetrate skin and have off-target biological effects.

The Role of Extracellular Vesicles in the Skin and Their Interactions with Nanoparticles.

Extracellular vesicles (EVs) include exosomes and microvesicles. They are released from cells under both physiological and pathological conditions. EVs can be isolated from a host of biological mediums, such as blood plasma, saliva, and skin.

Amorphous silicon dioxide nanoparticles modulate immune responses in a model of allergic contact dermatitis.

Amorphous silicon dioxide nanoparticles (SiNPs) are ubiquitous, and they are currently found in cosmetics, drugs, and foods. Biomedical research is also focused on using these nanoparticles as drug delivery and bio-sensing platforms. Due to the high potential for skin exposure to SiNPs, research into the effect of topical exposure on both healthy and inflammatory skin models is warranted.

Multi-walled carbon nanotube oxidation dependent keratinocyte cytotoxicity and skin inflammation.

Background: The effects of carbon nanotubes on skin toxicity have not been extensively studied; however, our lab has previously shown that a carboxylated multi-walled carbon nanotube (MWCNT) exacerbates the 2, 4-dinitrofluorobenzene induced contact hypersensitivity response in mice. Here we examine the role of carboxylation in MWCNT skin toxicity.

Results: MWCNTs were analyzed by transmission electron microscopy, zetasizer, and x-ray photoelectron spectroscopy to fully characterize the physical properties.

Effect of Nanoparticle Surface Coating on Cell Toxicity and Mitochondria Uptake.

We report on the effect of surface charge and the ligand coating composition of CdSe/ZnS core/shell quantum dot (QD) nanoparticles on human keratinocyte toxicity using fluorescent microscopy, flow cytometry, transmission electron microscopy. Two commonly reported positive charged (cysteamine, polyethylenimine) and two negative charged (glutathione, dihydrolipoic acid) ligands were studied. The QDs were fully characterized by UV-vis absorption spectroscopy, fluorescence emission spectroscopy, dynamic light scattering and zeta potential.

Immunomodulatory Effects of Nanoparticles on Skin Allergy.

In recent years there has been considerable effort to understand the interaction of nanomaterials with the skin. In this study we use an in vivo mouse model of allergic contact dermatitis to investigate how nanoparticles (NPs) may alter allergic responses in skin. We investigate a variety of NPs that vary in size, charge and composition.

In vivo quantification of quantum dot systemic transport in C57BL/6 hairless mice following skin application post-ultraviolet radiation.

Background: Previous work has demonstrated size, surface charge and skin barrier dependent penetration of nanoparticles into the viable layers of mouse skin. The goal of this work was to characterize the tissue distribution and mechanism of transport of nanoparticles beyond skin, with and without Ultraviolet Radiation (UVR) induced skin barrier disruption. Atomic absorption spectroscopy (AAS), flow cytometry and confocal microscopy were used to examine the effect of UVR dose (180 and 360 mJ/cm UVB) on the skin penetration and systemic distribution of quantum dot (QD) nanoparticles topically applied at different time-points post UVR using a hairless C57BL/6 mouse model.

Identifying drug resistant cancer cells using microbubble well arrays.

Drug resistance is a characteristic of tumor initiating cells that can give rise to metastatic disease. In this work we demonstrate the use of microbubble well arrays as a cell culture platform to enumerate and characterize drug resistant cells in a human derived tumorigenic squamous cell carcinoma cell line. The spherical architecture and compliant hydrophobic composition of the microbubble well favors single cell survival, clonal proliferation and formation of spheres that do not grow on standard tissue culture plastic and are resistant to cisplatin.

Nanoparticle-Enabled Transdermal Drug Delivery Systems for Enhanced Dose Control and Tissue Targeting.

Transdermal drug delivery systems have been around for decades, and current technologies (e.g., patches, ointments, and creams) enhance the skin permeation of low molecular weight, lipophilic drugs that are efficacious at low doses.

In vitro assays for determining the metastatic potential of melanoma cell lines with characterized in vivo invasiveness.

The metastatic potential of cancer cells is an elusive property that is indicative of the later stages of cancer progression. The ability to distinguish between poorly and highly metastatic cells is invaluable for understanding the basic biology of cancer and to develop more treatments. In this paper, we exploit a A375 melanoma cell line series (A375P, A375MA1, A375MA2) that vary in metastatic potential, to demonstrate an in vitro screening assay using polydimethylsiloxane (PDMS) microbubble well arrays that can distinguish these cell lines by their growth characteristics in including morphology, migratory potential, and clonogenic potential.

Impact of Cosmetic Lotions on Nanoparticle Penetration through C57BL/6 Hairless Mouse and Human Skin: A Comparison Study.

Understanding the interactions of nanoparticles (NPs) with skin is important from a consumer and occupational health and safety perspective, as well as for the design of effective NP-based transdermal therapeutics. Despite intense efforts to elucidate the conditions that permit NP penetration, there remains a lack of translatable results from animal models to human skin. The objectives of this study are to investigate the impact of common skin lotions on NP penetration and to quantify penetration differences of quantum dot (QD) NPs between freshly excised human and mouse skin.