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Article ; Online: PEGylation of Alternative MRI Contrast Agents Modulate Neutrophil Extracellular Trap Formation.

Snoderly, Hunter T / Freshwater, Kasey A / de la Torre, Celia Martinez / Panchal, Dhruvi M / Vito, Jenna N / Redigolo, Marcela L / Bennewitz, Margaret F

Microscopy and microanalysis : the official journal of Microscopy Society of America, Microbeam Analysis Society, Microscopical Society of Canada

2023 Volume 29, Issue 29 Suppl 1, Page(s) 1142–1143

Language	English
Publishing date	2023-08-23
Publishing country	England
Document type	Journal Article
ZDB-ID	1385710-1
ISSN	1435-8115 ; 1431-9276
ISSN (online)	1435-8115
ISSN	1431-9276
DOI	10.1093/micmic/ozad067.584
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Article ; Online: Caveat Emptor: Commercialized Manganese Oxide Nanoparticles Exhibit Unintended Properties.

Martinez de la Torre, Celia / Freshwater, Kasey A / Looney-Sanders, Mara A / Wang, Qiang / Bennewitz, Margaret F

ACS omega

2023 Volume 8, Issue 21, Page(s) 18799–18810

Abstract: Nano-encapsulated manganese oxide (NEMO) particles are noteworthy contrast agents for magnetic resonance imaging (MRI) due to their bright, pH-switchable signal ("OFF" to "ON" at low pH), high metal loading, and targeting capability for increased ... ...

Abstract	Nano-encapsulated manganese oxide (NEMO) particles are noteworthy contrast agents for magnetic resonance imaging (MRI) due to their bright, pH-switchable signal ("OFF" to "ON" at low pH), high metal loading, and targeting capability for increased specificity. For the first time, we performed a head-to-head comparison of NEMO particles from In-house and commercialized sources (US Nano vs Nanoshel) to assess their potential as bright T
Language	English
Publishing date	2023-05-18
Publishing country	United States
Document type	Journal Article
ISSN	2470-1343
ISSN (online)	2470-1343
DOI	10.1021/acsomega.3c00892
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Article ; Online: Manganese Oxide Nanoparticle Synthesis by Thermal Decomposition of Manganese(II) Acetylacetonate.

Martinez de la Torre, Celia / Bennewitz, Margaret F

Journal of visualized experiments : JoVE

2020 , Issue 160

Abstract: For biomedical applications, metal oxide nanoparticles such as iron oxide and manganese oxide (MnO), have been used as biosensors and contrast agents in magnetic resonance imaging (MRI). While iron oxide nanoparticles provide constant negative contrast ... ...

Abstract	For biomedical applications, metal oxide nanoparticles such as iron oxide and manganese oxide (MnO), have been used as biosensors and contrast agents in magnetic resonance imaging (MRI). While iron oxide nanoparticles provide constant negative contrast on MRI over typical experimental timeframes, MnO generates switchable positive contrast on MRI through dissolution of MnO to Mn
MeSH term(s)	Glass/chemistry ; Hydrophobic and Hydrophilic Interactions ; Hydroxybutyrates/chemistry ; Manganese/chemistry ; Manganese Compounds/chemistry ; Metal Nanoparticles/chemistry ; Metal Nanoparticles/ultrastructure ; Nitrogen/chemistry ; Oxides/chemistry ; Particle Size ; Pentanones/chemistry ; Spectroscopy, Fourier Transform Infrared ; Surface Properties ; Temperature ; Water/chemistry ; X-Ray Diffraction
Chemical Substances	Hydroxybutyrates ; Manganese Compounds ; Oxides ; Pentanones ; Water (059QF0KO0R) ; acetyl acetonate (17272-66-1) ; Manganese (42Z2K6ZL8P) ; manganese oxide (64J2OA7MH3) ; Nitrogen (N762921K75)
Language	English
Publishing date	2020-06-18
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Video-Audio Media
ZDB-ID	2259946-0
ISSN	1940-087X ; 1940-087X
ISSN (online)	1940-087X
ISSN	1940-087X
DOI	10.3791/61572
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Article ; Online: E-Cigarette Use: Device Market, Study Design, and Emerging Evidence of Biological Consequences.

Snoderly, Hunter T / Nurkiewicz, Timothy R / Bowdridge, Elizabeth C / Bennewitz, Margaret F

International journal of molecular sciences

2021 Volume 22, Issue 22

Abstract: Electronic cigarettes are frequently viewed as a safer alternative to conventional cigarettes; however, evidence to support this perspective has not materialized. Indeed, the current literature reports that electronic cigarette use is associated with ... ...

Abstract	Electronic cigarettes are frequently viewed as a safer alternative to conventional cigarettes; however, evidence to support this perspective has not materialized. Indeed, the current literature reports that electronic cigarette use is associated with both acute lung injury and subclinical dysfunction to the lung and vasculature that may result in pathology following chronic use. E-cigarettes can alter vascular dynamics, polarize innate immune populations towards a proinflammatory state, compromise barrier function in the pulmonary endothelium and epithelium, and promote pre-oncogenic phenomena. This review will summarize the variety of e-cigarette products available to users, discuss current challenges in e-cigarette study design, outline the range of pathologies occurring in cases of e-cigarette associated acute lung injury, highlight disease supporting tissue- and cellular-level changes resulting from e-cigarette exposure, and briefly examine how these changes may promote tumorigenesis. Continued research of the mechanisms by which e-cigarettes induce pathology benefit users and clinicians by resulting in increased regulation of vaping devices, informing treatments for emerging diseases e-cigarettes produce, and increasing public awareness to reduce e-cigarette use and the onset of preventable disease.
MeSH term(s)	Acute Lung Injury/chemically induced ; Acute Lung Injury/immunology ; Acute Lung Injury/pathology ; Animals ; Blood Platelets/drug effects ; Blood Platelets/immunology ; Blood Platelets/pathology ; Carcinogenesis/immunology ; Carcinogenesis/pathology ; Cardiovascular Diseases/chemically induced ; Cardiovascular Diseases/immunology ; Cardiovascular Diseases/pathology ; Cytokines/biosynthesis ; Cytokines/immunology ; Electronic Nicotine Delivery Systems ; Humans ; Immunity, Innate/drug effects ; Lung/drug effects ; Lung/immunology ; Lung/pathology ; Lung Neoplasms/chemically induced ; Lung Neoplasms/immunology ; Lung Neoplasms/pathology ; Macrophages/drug effects ; Macrophages/immunology ; Macrophages/pathology ; Neovascularization, Pathologic/chemically induced ; Neovascularization, Pathologic/immunology ; Neovascularization, Pathologic/pathology ; Neutrophils/drug effects ; Neutrophils/immunology ; Neutrophils/pathology ; Reactive Oxygen Species/immunology ; Reactive Oxygen Species/metabolism ; Respiratory Mucosa/drug effects ; Respiratory Mucosa/immunology ; Respiratory Mucosa/pathology ; Rodentia ; Vaping/immunology ; Vaping/pathology
Chemical Substances	Cytokines ; Reactive Oxygen Species
Language	English
Publishing date	2021-11-18
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms222212452
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Article ; Online: Neutrophil extracellular traps in breast cancer and beyond: current perspectives on NET stimuli, thrombosis and metastasis, and clinical utility for diagnosis and treatment.

Snoderly, Hunter T / Boone, Brian A / Bennewitz, Margaret F

Breast cancer research : BCR

2019 Volume 21, Issue 1, Page(s) 145

Abstract: The formation of neutrophil extracellular traps (NETs), known as NETosis, was first observed as a novel immune response to bacterial infection, but has since been found to occur abnormally in a variety of other inflammatory disease states including ... ...

Abstract	The formation of neutrophil extracellular traps (NETs), known as NETosis, was first observed as a novel immune response to bacterial infection, but has since been found to occur abnormally in a variety of other inflammatory disease states including cancer. Breast cancer is the most commonly diagnosed malignancy in women. In breast cancer, NETosis has been linked to increased disease progression, metastasis, and complications such as venous thromboembolism. NET-targeted therapies have shown success in preclinical cancer models and may prove valuable clinical targets in slowing or halting tumor progression in breast cancer patients. We will briefly outline the mechanisms by which NETs may form in the tumor microenvironment and circulation, including the crosstalk between neutrophils, tumor cells, endothelial cells, and platelets as well as the role of cancer-associated extracellular vesicles in modulating neutrophil behavior and NET extrusion. The prognostic implications of cancer-associated NETosis will be explored in addition to development of novel therapeutics aimed at targeting NET interactions to improve outcomes in patients with breast cancer.
MeSH term(s)	Biomarkers ; Breast Neoplasms/diagnosis ; Breast Neoplasms/etiology ; Breast Neoplasms/metabolism ; Breast Neoplasms/therapy ; Disease Management ; Extracellular Traps/immunology ; Extracellular Traps/metabolism ; Female ; Humans ; Molecular Targeted Therapy ; Neoplasm Metastasis ; Neoplasm Staging ; Neutrophils/immunology ; Neutrophils/metabolism ; Neutrophils/pathology ; Thrombosis ; Tumor Microenvironment
Chemical Substances	Biomarkers
Language	English
Publishing date	2019-12-18
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2015059-3
ISSN	1465-542X ; 1465-5411
ISSN (online)	1465-542X
ISSN	1465-5411
DOI	10.1186/s13058-019-1237-6
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Zs.A 5494: Show issues

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Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

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Article ; Online: Live Imaging of the Lung.

Brzoska, Tomasz / Kaminski, Tomasz W / Bennewitz, Margaret F / Sundd, Prithu

Current protocols in cytometry

2020 Volume 95, Issue 1, Page(s) e80

Abstract: Live imaging is critical to determining the dynamics and spatial interactions of cells within the tissue environment. In the lung, this has proven to be difficult due to the motion brought about by ventilation and cardiac contractions. A previous version ...

Abstract	Live imaging is critical to determining the dynamics and spatial interactions of cells within the tissue environment. In the lung, this has proven to be difficult due to the motion brought about by ventilation and cardiac contractions. A previous version of this Current Protocols in Cytometry article reported protocols for imaging ex vivo live lung slices and the intact mouse lung. Here, we update those protocols by adding new methodologies, new approaches for quantitative image analysis, and new areas of potential application. © 2020 Wiley Periodicals LLC. Basic Protocol 1: Live imaging of lung slices Support Protocol 1: Staining lung sections with fluorescent antibodies Basic Protocol 2: Live imaging in the mouse lung Support Protocol 2: Intratracheal instillations Support Protocol 3: Intravascular instillations Support Protocol 4: Monitoring vital signs of the mouse during live lung imaging Support Protocol 5: Antibodies Support Protocol 6: Fluorescent reporter mice Basic Protocol 3: Quantification of neutrophil-platelet aggregation in pulmonary vasculature Basic Protocol 4: Quantification of platelet-dependent pulmonary thrombosis Basic Protocol 5: Quantification of pulmonary vascular permeability.
MeSH term(s)	Animals ; Diagnostic Imaging/methods ; Lung/diagnostic imaging ; Mice ; Staining and Labeling
Language	English
Publishing date	2020-10-07
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2179050-4
ISSN	1934-9300 ; 1934-9297
ISSN (online)	1934-9300
ISSN	1934-9297
DOI	10.1002/cpcy.80
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Article ; Online: PEGylation of Metal Oxide Nanoparticles Modulates Neutrophil Extracellular Trap Formation.

Snoderly, Hunter T / Freshwater, Kasey A / Martinez de la Torre, Celia / Panchal, Dhruvi M / Vito, Jenna N / Bennewitz, Margaret F

Biosensors

2022 Volume 12, Issue 2

Abstract: Novel metal oxide nanoparticle (NP) contrast agents may offer safety and functionality advantages over conventional gadolinium-based contrast agents (GBCAs) for cancer diagnosis by magnetic resonance imaging. However, little is known about the behavior ... ...

Abstract	Novel metal oxide nanoparticle (NP) contrast agents may offer safety and functionality advantages over conventional gadolinium-based contrast agents (GBCAs) for cancer diagnosis by magnetic resonance imaging. However, little is known about the behavior of metal oxide NPs, or of their effect, upon coming into contact with the innate immune system. As neutrophils are the body's first line of defense, we sought to understand how manganese oxide and iron oxide NPs impact leukocyte functionality. Specifically, we evaluated whether contrast agents caused neutrophils to release web-like fibers of DNA known as neutrophil extracellular traps (NETs), which are known to enhance metastasis and thrombosis in cancer patients. Murine neutrophils were treated with GBCA, bare manganese oxide or iron oxide NPs, or poly(lactic-co-glycolic acid) (PLGA)-coated metal oxide NPs with different incorporated levels of poly(ethylene glycol) (PEG). Manganese oxide NPs elicited the highest NETosis rates and had enhanced neutrophil uptake properties compared to iron oxide NPs. Interestingly, NPs with low levels of PEGylation produced more NETs than those with higher PEGylation. Despite generating a low rate of NETosis, GBCA altered neutrophil cytokine expression more than NP treatments. This study is the first to investigate whether manganese oxide NPs and GBCAs modulate NETosis and reveals that contrast agents may have unintended off-target effects which warrant further investigation.
MeSH term(s)	Animals ; Contrast Media ; Extracellular Traps ; Humans ; Metal Nanoparticles ; Mice ; Nanoparticles ; Neutrophils/metabolism ; Oxides
Chemical Substances	Contrast Media ; Oxides
Language	English
Publishing date	2022-02-16
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662125-3
ISSN	2079-6374 ; 2079-6374
ISSN (online)	2079-6374
ISSN	2079-6374
DOI	10.3390/bios12020123
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Article: Short-term exposure of female BALB/cJ mice to e-cigarette aerosol promotes neutrophil recruitment and enhances neutrophil-platelet aggregation in pulmonary microvasculature.

Snoderly, Hunter T / Alkhadrawi, Hassan / Panchal, Dhruvi M / Weaver, Kelly L / Vito, Jenna N / Freshwater, Kasey A / Santiago, Stell P / Olfert, I Mark / Nurkiewicz, Timothy R / Bennewitz, Margaret F

Journal of toxicology and environmental health. Part A

2023 Volume 86, Issue 8, Page(s) 246–262

Abstract: Despite the perception that e-cigarettes are safer than conventional cigarettes, numerous findings demonstrated that e-cigarette aerosol (EC) exposure induced compromised immune functionality, vascular changes even after acute exposure, and lung injury. ... ...

Abstract	Despite the perception that e-cigarettes are safer than conventional cigarettes, numerous findings demonstrated that e-cigarette aerosol (EC) exposure induced compromised immune functionality, vascular changes even after acute exposure, and lung injury. Notably, altered neutrophil functionality and platelet hemodynamics have been observed post-EC exposure. It was hypothesized that EC exposure initiates an inflammatory response resulting in altered neutrophil behavior and increased neutrophil-platelet interaction in the pulmonary microvasculature. Neutrophil and platelet responses were examined up to 48 hrs following whole-body, short-term EC exposure without flavorants or nicotine in a murine model, which most closely modeled secondhand exposure. This study is the first to investigate the impact of EC exposure through lung intravital imaging. Compared to room air-exposed mice, EC-exposed mice displayed significantly increased 1.7‒1.9-fold number of neutrophils in the pulmonary microvasculature associated with no marked change in neutrophils within whole blood or bronchoalveolar lavage fluid (BALF). Neutrophil-platelet interactions were also significantly elevated 1.9‒2.5-fold in exposed mice. Plasma concentration of myeloperoxidase was markedly reduced 1.5-fold 48 hr following exposure cessation, suggesting suppressed neutrophil antimicrobial activity. Cytokine expression exhibited changes indicating vascular damage. Effects persisted for 48 hr post-EC exposure. Data demonstrated that EC exposure repeated for 3 consecutive days in 2.5 hr intervals in the absence of flavorants or nicotine resulted in modified pulmonary vasculature hemodynamics, altered immune functionality, and a pro-inflammatory state in female BALB/cJ mice.
MeSH term(s)	Female ; Mice ; Animals ; Neutrophils/metabolism ; Electronic Nicotine Delivery Systems ; Platelet Aggregation ; Nicotine/metabolism ; Neutrophil Infiltration ; Respiratory Aerosols and Droplets ; Lung/metabolism ; Microvessels
Chemical Substances	Nicotine (6M3C89ZY6R)
Language	English
Publishing date	2023-03-01
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't
ZDB-ID	1413345-3
ISSN	1528-7394 ; 0098-4108 ; 1087-2620
ISSN	1528-7394 ; 0098-4108 ; 1087-2620
DOI	10.1080/15287394.2023.2184738
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Zs.A 1268: Show issues

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ab Jg. 2022: Lesesaal (EG)

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Article ; Online: Tuning the size and composition of manganese oxide nanoparticles through varying temperature ramp and aging time.

Martinez de la Torre, Celia / Grossman, Jasmine H / Bobko, Andrey A / Bennewitz, Margaret F

PloS one

2020 Volume 15, Issue 9, Page(s) e0239034

Abstract: Manganese oxide (MnO) nanoparticles (NPs) can serve as robust pH-sensitive contrast agents for magnetic resonance imaging (MRI) due to Mn2+ release at low pH, which generates a ~30 fold change in T1 relaxivity. Strategies to control NP size, composition, ...

Abstract	Manganese oxide (MnO) nanoparticles (NPs) can serve as robust pH-sensitive contrast agents for magnetic resonance imaging (MRI) due to Mn2+ release at low pH, which generates a ~30 fold change in T1 relaxivity. Strategies to control NP size, composition, and Mn2+ dissolution rates are essential to improve diagnostic performance of pH-responsive MnO NPs. We are the first to demonstrate that MnO NP size and composition can be tuned by the temperature ramping rate and aging time used during thermal decomposition of manganese(II) acetylacetonate. Two different temperature ramping rates (10°C/min and 20°C/min) were applied to reach 300°C and NPs were aged at that temperature for 5, 15, or 30 min. A faster ramping rate and shorter aging time produced the smallest NPs of ~23 nm. Shorter aging times created a mixture of MnO and Mn3O4 NPs, whereas longer aging times formed MnO. Our results indicate that a 20°C/min ramp rate with an aging time of 30 min was the ideal temperature condition to form the smallest pure MnO NPs of ~32 nm. However, Mn2+ dissolution rates at low pH were unaffected by synthesis conditions. Although Mn2+ production was high at pH 5 mimicking endosomes inside cells, minimal Mn2+ was released at pH 6.5 and 7.4, which mimic the tumor extracellular space and blood, respectively. To further elucidate the effects of NP composition and size on Mn2+ release and MRI contrast, the ideal MnO NP formulation (~32 nm) was compared with smaller MnO and Mn3O4 NPs. Small MnO NPs produced the highest amount of Mn2+ at acidic pH with maximum T1 MRI signal; Mn3O4 NPs generated the lowest MRI signal. MnO NPs encapsulated within poly(lactide-co-glycolide) (PLGA) retained significantly higher Mn2+ release and MRI signal compared to PLGA Mn3O4 NPs. Therefore, MnO instead of Mn3O4 should be targeted intracellularly to maximize MRI contrast.
MeSH term(s)	Contrast Media/chemistry ; Magnetic Resonance Imaging/methods ; Manganese Compounds/chemistry ; Metal Nanoparticles/chemistry ; Nanoparticles/chemistry ; Oxides/chemistry ; Temperature ; Time Factors
Chemical Substances	Contrast Media ; Manganese Compounds ; Oxides ; manganese oxide (64J2OA7MH3)
Language	English
Publishing date	2020-09-18
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0239034
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Article ; Online: P-selectin-deficient mice to study pathophysiology of sickle cell disease.

Bennewitz, Margaret F / Tutuncuoglu, Egemen / Gudapati, Shweta / Brzoska, Tomasz / Watkins, Simon C / Monga, Satdarshan P / Pradhan-Sundd, Tirthadipa / Sundd, Prithu

Blood advances

2020 Volume 4, Issue 2, Page(s) 266–273

MeSH term(s)	Anemia, Sickle Cell/physiopathology ; Animals ; Humans ; Male ; Mice ; P-Selectin/deficiency ; Rats
Chemical Substances	P-Selectin
Language	English
Publishing date	2020-01-17
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2915908-8
ISSN	2473-9537 ; 2473-9529
ISSN (online)	2473-9537
ISSN	2473-9529
DOI	10.1182/bloodadvances.2019000603
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Zs.A 7153: Show issues

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