18 results on '"Anna E. Czapar"'
Search Results
2. Clinical characteristics of hospitalized patients with false-negative severe acute respiratory coronavirus virus 2 (SARS-CoV-2) test results
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Maggie Collison, Eleanor E. Friedman, Antigone Kraft, Bennett J Waxse, Anna E Czapar, Dariusz A Hareza, Jessica P Ridgway, and Erica L. MacKenzie
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0301 basic medicine ,Microbiology (medical) ,medicine.medical_specialty ,Epidemiology ,030106 microbiology ,Vital signs ,Anosmia ,Logistic regression ,medicine.disease_cause ,03 medical and health sciences ,COVID-19 Testing ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,030212 general & internal medicine ,Retrospective Studies ,Coronavirus ,SARS-CoV-2 ,business.industry ,COVID-19 ,Odds ratio ,Confidence interval ,Test (assessment) ,Infectious Diseases ,Original Article ,medicine.symptom ,business ,Cohort study - Abstract
Objective:To determine clinical characteristics associated with false-negative severe acute respiratory coronavirus virus 2 (SARS-CoV-2) test results to help inform coronavirus disease 2019 (COVID-19) testing practices in the inpatient setting.Design:A retrospective observational cohort study.Setting:Tertiary-care facility.Patients:All patients 2 years of age and older tested for SARS-CoV-2 between March 14, 2020, and April 30, 2020, who had at least 2 SARS-CoV-2 reverse-transcriptase polymerase chain reaction tests within 7 days.Methods:The primary outcome measure was a false-negative testing episode, which we defined as an initial negative test followed by a positive test within the subsequent 7 days. Data collected included symptoms, demographics, comorbidities, vital signs, labs, and imaging studies. Logistic regression was used to model associations between clinical variables and false-negative SARS-CoV-2 test results.Results:Of the 1,009 SARS-CoV-2 test results included in the analysis, 4.0% were false-negative results. In multivariable regression analysis, compared with true-negative test results, false-negative test results were associated with anosmia or ageusia (adjusted odds ratio [aOR], 8.4; 95% confidence interval [CI], 1.4–50.5; P = .02), having had a COVID-19–positive contact (aOR, 10.5; 95% CI, 4.3–25.4; P < .0001), and having an elevated lactate dehydrogenase level (aOR, 3.3; 95% CI, 1.2–9.3; P = .03). Demographics, symptom duration, other laboratory values, and abnormal chest imaging were not significantly associated with false-negative test results in our multivariable analysis.Conclusions:Clinical features can help predict which patients are more likely to have false-negative SARS-CoV-2 test results.
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- 2021
3. Radiation Therapy Combined with Cowpea Mosaic Virus Nanoparticle in Situ Vaccination Initiates Immune-Mediated Tumor Regression
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Anna E. Czapar, Nancy L. Oleinick, Steven Fiering, Nicole F. Steinmetz, and Ravi Patel
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0301 basic medicine ,General Chemical Engineering ,medicine.medical_treatment ,Article ,lcsh:Chemistry ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Ovarian carcinoma ,Medicine ,biology ,business.industry ,Tumor-infiltrating lymphocytes ,Cowpea mosaic virus ,General Chemistry ,medicine.disease ,biology.organism_classification ,3. Good health ,Radiation therapy ,Vaccination ,030104 developmental biology ,lcsh:QD1-999 ,030220 oncology & carcinogenesis ,Cancer research ,Immunohistochemistry ,business ,Ovarian cancer - Abstract
Epithelial ovarian cancer is a deadly gynecologic malignancy because of its late detection, usually after local and distant metastatic spread. These cancers develop resistance to traditional chemotherapeutic agents; therefore, the development of next-generation immunotherapeutic approaches may have a significant promise in improving outcomes. A novel immunotherapeutic approach utilizing combination radiation therapy (RT) with immunostimulatory cowpea mosaic virus (CPMV) was tested in a preclinical syngeneic mouse model of ovarian carcinoma. ID8-Defb29/Vegf tumors were generated in C57BL/6 mice. Compared to placebo-treated control tumors or those treated with a single agent RT or CPMV, the combination treatment resulted in a significantly improved tumor growth delay (p < 0.05). Additionally, immunohistochemical profiling of tumor samples after treatment with CPMV demonstrated an increase in tumor infiltrating lymphocytes (TILs). These results suggest that utilizing CPMV particles in combination with RT can turn an immunologically “cold” tumor (with low number of TILs) into an immunologically “hot” tumor. This novel combination treatment approach of RT and CPMV demonstrated the ability to control tumor growth in a preclinical ID8 ovarian cancer model, showing promise as an in situ tumor vaccine and warrants further testing.
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- 2018
4. Plant viruses and bacteriophages for drug delivery in medicine and biotechnology
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Anna E. Czapar and Nicole F. Steinmetz
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0301 basic medicine ,Nanotechnology ,02 engineering and technology ,Biology ,Biochemistry ,Article ,Plant Viruses ,Analytical Chemistry ,03 medical and health sciences ,Human health ,Drug Delivery Systems ,Atomic resolution ,Plant virus ,Animals ,Humans ,Bacteriophages ,business.industry ,021001 nanoscience & nanotechnology ,Biocompatible material ,3. Good health ,Biotechnology ,030104 developmental biology ,Drug delivery ,Medicine ,0210 nano-technology ,business - Abstract
There are a wide variety of synthetic and naturally occurring nanomaterials under development for nanoscale cargo-delivery applications. Viruses play a special role in these developments, because they can be regarded as naturally occurring nanomaterials evolved to package and deliver cargos. While any nanomaterial has its advantage and disadvantages, viral nanoparticles (VNPs), in particular the ones derived from plant viruses and bacteriophages, are attractive options for cargo-delivery as they are biocompatible, biodegradable, and non-infectious to mammals. Their protein-based structures are often understood at atomic resolution and are amenable to modification with atomic-level precision through chemical and genetic engineering. Here we present a focused review of the emerging technology development of plant viruses and bacteriophages targeting human health and agricultural applications. Key target areas of development are their use in chemotherapy-, photodynamic therapy-, pesticide-delivery, gene therapy, vaccine carriers, and immunotherapy.
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- 2017
5. Tobacco mosaic virus-based protein nanoparticles and nanorods for chemotherapy delivery targeting breast cancer
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Lauren N. Randolph, Anna E. Czapar, Michael A. Bruckman, Nicole F. Steinmetz, and Allen VanMeter
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Cell Survival ,Surface Properties ,viruses ,Lysine ,Pharmaceutical Science ,Antineoplastic Agents ,Breast Neoplasms ,Nanotechnology ,02 engineering and technology ,010402 general chemistry ,01 natural sciences ,Article ,Drug Delivery Systems ,Plant virus ,Aspartic acid ,Tobacco mosaic virus ,Humans ,Medicine ,Doxorubicin ,Particle Size ,Nanotubes ,Bioconjugation ,business.industry ,fungi ,food and beverages ,021001 nanoscience & nanotechnology ,3. Good health ,0104 chemical sciences ,Tobacco Mosaic Virus ,Targeted drug delivery ,Biochemistry ,Drug delivery ,MCF-7 Cells ,Nanoparticles ,Capsid Proteins ,Female ,0210 nano-technology ,business ,medicine.drug - Abstract
Drug delivery systems are required for drug targeting to avoid adverse effects associated with chemotherapy treatment regimes. Our approach is focused on the study and development of plant virus-based materials as drug delivery systems; specifically, this work focuses on the tobacco mosaic virus (TMV). Native TMV forms a hollow, high aspect-ratio nanotube measuring 300 × 18 nm with a 4 nm-wide central channel. Heat-transformation can be applied to TMV yielding spherical nanoparticles (SNPs) measuring ~50 nm in size. While bioconjugate chemistries have been established to modify the TMV rod, such methods have not yet been described for the SNP platform. In this work, we probed the reactivity of SNPs toward bioconjugate reactions targeting lysine, glutamine/aspartic acid, and cysteine residues. We demonstrate functionalization of SNPs using these chemistries yielding efficient payload conjugation. In addition to covalent labeling techniques, we developed encapsulation techniques, where the cargo is loaded into the SNP during heat-transition from rod-to-sphere. Finally, we developed TMV and SNP formulations loaded with the chemotherapeutic doxorubicin, and we demonstrate the application of TMV rods and spheres for chemotherapy delivery targeting breast cancer.
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- 2016
6. The in vivo fates of plant viral nanoparticles camouflaged using self-proteins: overcoming immune recognition
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Anna E. Czapar, Phoebe L. Stewart, Nicole F. Steinmetz, Neetu M. Gulati, and Andrzej S. Pitek
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0301 basic medicine ,viruses ,Biomedical Engineering ,Serum albumin ,02 engineering and technology ,Article ,03 medical and health sciences ,Immune system ,In vivo ,Lysosome ,medicine ,Tobacco mosaic virus ,General Materials Science ,biology ,Chemistry ,fungi ,food and beverages ,General Chemistry ,General Medicine ,021001 nanoscience & nanotechnology ,Cell biology ,Antibody opsonization ,030104 developmental biology ,medicine.anatomical_structure ,biology.protein ,Antibody ,0210 nano-technology ,Linker - Abstract
Nanoparticles offer a promising avenue for targeted delivery of therapies. To slow clearance, nanoparticles are frequently stealth-coated to prevent opsonization and immune recognition. Serum albumin (SA) has been used as a bio-inspired stealth coating. To develop this shielding strategy for clinical applications, it is critical to understand the interactions between the immune system and SA-camouflaged nanoparticles. This work investigates the in vivo processing of SA-coated nanoparticles using tobacco mosaic virus (TMV) as a model system. In comparing four different SA-formulations, the particles with high SA coverage conjugated to TMV via a short linker performed the best at preventing antibody recognition. Irrelevant of the coating chemistry, all formulations led to similar levels of TMV-specific antibodies after repeat administration in mice; importantly though, SA-specific antibodies were not detected and the TMV-specific antibodies were unable to recognize shielded SA-coated TMV. Upon uptake in macrophages, the shielding agent and nanoparticle separate, where TMV trafficked to the lysosome and SA appears to recycle. The distinct intracellular fates of the TMV carrier and SA shielding agent explain why anti-TMV but not SA-specific antibodies are generated. This work characterizes the outcomes of SA-camouflaged TMV after immune recognition, and highlights the effectiveness of SA as a nanoparticle shielding agent.
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- 2018
7. Drug-Loaded Plant-Virus Based Nanoparticles for Cancer Drug Delivery
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Michael A, Bruckman, Anna E, Czapar, and Nicole F, Steinmetz
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Tobacco Mosaic Virus ,Drug Delivery Systems ,Doxorubicin ,Neoplasms ,Humans ,Nanoparticles ,Antineoplastic Agents - Abstract
Nature has designed nanosized particles, specifically viruses, equipped to deliver cargo to cells. We report the chemical bioconjugation and shape shifting of a hollow, rod-shaped tobacco mosaic virus (TMV) to dense spherical nanoparticles (SNPs). We describe methods to transform TMV rods to spheres, load TMV rods and spheres with the chemotherapeutic drug, doxorubicin (DOX), to deliver modified particles to breast cancer cells, and to determine the IC
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- 2018
8. Speciation of Phenanthriplatin and its Analogs in the Core of Tobacco Mosaic Virus
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Stephen J. Lippard, Amit A. Vernekar, David Wang, Anna E. Czapar, Frank A. Veliz, Nicole F. Steinmetz, and Gilles Berger
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Models, Molecular ,Organoplatinum Compounds ,media_common.quotation_subject ,Ionic bonding ,02 engineering and technology ,Biochemistry ,Catalysis ,Article ,Adduct ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Colloid and Surface Chemistry ,Tobacco mosaic virus ,Molecule ,Reactivity (chemistry) ,media_common ,Molecular Structure ,Phenanthriplatin ,General Chemistry ,021001 nanoscience & nanotechnology ,Phenanthridines ,Tobacco Mosaic Virus ,Speciation ,chemistry ,Covalent bond ,030220 oncology & carcinogenesis ,Biophysics ,0210 nano-technology - Abstract
Efficient loading of drugs in novel delivery agents has the potential to substantially improve therapy by targeting the diseased tissue while avoiding unwanted side effects. Here we report the first systematic study of the loading mechanism of phenanthriplatin and its analogs into tobacco mosaic virus (TMV), previously used by our group as an efficient carrier for anticancer drug delivery. A detailed investigation of the preferential uptake of phenanthriplatin in its aquated form (∼2000 molecules per TMV particle versus ∼1000 for the chlorido form) is provided. Whereas the net charge of phenanthriplatin analogs and their ionic mobilities have no effect on loading, the reactivity of aqua phenanthriplatin with the glutamates, lining the interior walls of the channel of TMV, has a pronounced effect on its loading. MALDI-MS analysis along with NMR spectroscopic studies of a model reaction of hydroxy-phenanthriplatin with acetate establish the formation of stable covalent adducts. The increased number of heteroaromatic rings on the platinum ligand appears to enhance loading, possibly by stabilizing hydrophobic stacking interactions with TMV core components, specifically Pro102 and Thr103 residues neighboring Glu97 and Glu106 in the channel. Electron transfer dissociation MS/MS fragmentation, a technique that can prevent mass-condition-vulnerable modification of proteins, reveals that Glu97 preferentially participates over Glu106 in covalent bond formation to the platinum center.
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- 2018
9. Drug-Loaded Plant-Virus Based Nanoparticles for Cancer Drug Delivery
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Michael A. Bruckman, Nicole F. Steinmetz, and Anna E. Czapar
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0301 basic medicine ,Drug ,Bioconjugation ,genetic structures ,Chemistry ,viruses ,media_common.quotation_subject ,fungi ,food and beverages ,Nanoparticle ,02 engineering and technology ,021001 nanoscience & nanotechnology ,03 medical and health sciences ,030104 developmental biology ,Plant virus ,Drug delivery ,medicine ,Tobacco mosaic virus ,Biophysics ,Cancer drug delivery ,Doxorubicin ,sense organs ,0210 nano-technology ,medicine.drug ,media_common - Abstract
Nature has designed nanosized particles, specifically viruses, equipped to deliver cargo to cells. We report the chemical bioconjugation and shape shifting of a hollow, rod-shaped tobacco mosaic virus (TMV) to dense spherical nanoparticles (SNPs). We describe methods to transform TMV rods to spheres, load TMV rods and spheres with the chemotherapeutic drug, doxorubicin (DOX), to deliver modified particles to breast cancer cells, and to determine the IC50 values of the plant virus-based drug delivery system.
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- 2018
10. Slow-Release Formulation of Cowpea Mosaic Virus for In Situ Vaccine Delivery to Treat Ovarian Cancer
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Anna E. Czapar, Nicole F. Steinmetz, Brylee David B. Tiu, Jonathan K. Pokorski, and Frank A. Veliz
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In situ ,General Chemical Engineering ,medicine.medical_treatment ,General Physics and Astronomy ,Medicine (miscellaneous) ,02 engineering and technology ,Pharmacology ,Biochemistry, Genetics and Molecular Biology (miscellaneous) ,03 medical and health sciences ,0302 clinical medicine ,Cancer immunotherapy ,Slow Release Formulation ,medicine ,General Materials Science ,cancer immunotherapy ,biology ,Full Paper ,Chemistry ,Cowpea mosaic virus ,General Engineering ,viral nanoparticles ,Single injection ,Immunotherapy ,Vaccine delivery ,Full Papers ,in situ vaccines ,slow release therapeutics ,021001 nanoscience & nanotechnology ,biology.organism_classification ,medicine.disease ,3. Good health ,cowpea mosaic virus ,030220 oncology & carcinogenesis ,0210 nano-technology ,Ovarian cancer - Abstract
The plant viral nanoparticle cowpea mosaic virus (CPMV) is shown to be an effective immunotherapy for ovarian cancer when administered as in situ vaccine weekly, directly into the intraperitoneal (IP) space in mice with disseminated tumors. While the antitumor efficacy is promising, the required frequency of administration may pose challenges for clinical implementation. To overcome this, a slow release formulation is developed. CPMV and polyamidoamine generation 4 dendrimer form aggregates (CPMV‐G4) based on electrostatic interactions and as a function of salt concentration, allowing for tailoring of aggregate size and release of CPMV. The antitumor efficacy of a single administration of CPMV‐G4 is compared to weekly administration of soluble CPMV in a mouse model of peritoneal ovarian cancer and found to be as effective at reducing disease burden as more frequent administrations of soluble CPMV; a single injection of soluble CPMV, does not significantly slow cancer development. The ability of CPMV‐G4 to control tumor growth following a single injection is likely due to the continued presence of CPMV in the IP space leading to prolonged immune stimulation. This enhanced retention of CPMV and its antitumor efficacy demonstrates the potential for viral–dendrimer hybrids to be used for delayed release applications.
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- 2017
11. Interface of Physics and Biology: Engineering Virus-Based Nanoparticles for Biophotonics
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Antonio De Luca, Nicole F. Steinmetz, Amy M. Wen, Anna E. Czapar, Melissa Infusino, Giuseppe Strangi, and Daniel L. Kernan
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Models, Molecular ,Optical Phenomena ,Protein Conformation ,Comovirus ,Biomedical Engineering ,Stacking ,Pharmaceutical Science ,Nanoparticle ,Bioengineering ,Nanotechnology ,02 engineering and technology ,010402 general chemistry ,01 natural sciences ,Article ,Engineering ,Humans ,Fluorescent Dyes ,Pharmacology ,biology ,Chemistry ,Organic Chemistry ,Cowpea mosaic virus ,021001 nanoscience & nanotechnology ,biology.organism_classification ,Fluorescence ,Molecular Imaging ,0104 chemical sciences ,3. Good health ,Tobacco Mosaic Virus ,Biophotonics ,Optical phenomena ,Nanoparticles ,Surface modification ,Capsid Proteins ,Molecular imaging ,0210 nano-technology ,HeLa Cells ,Biotechnology - Abstract
Virus-based nanoparticles (VNPs) have been used for a wide range of applications, spanning basic materials science and translational medicine. Their propensity to self-assemble into precise structures that offer a three-dimensional scaffold for functionalization has led to their use as optical contrast agents and related biophotonics applications. A number of fluorescently labeled platforms have been developed and their utility in optical imaging demonstrated, yet their optical properties have not been investigated in detail. In this study, two VNPs of varying architectures were compared side-by-side to determine the impact of dye density, dye localization, conjugation chemistry, and microenvironment on the optical properties of the probes. Dyes were attached to icosahedral cowpea mosaic virus (CPMV) and rod-shaped tobacco mosaic virus (TMV) through a range of chemistries to target particular side chains displayed at specific locations around the virus. The fluorescence intensity and lifetime of the particles were determined, first using photochemical experiments on the benchtop, and second in imaging experiments using tissue culture experiments. The virus-based optical probes were found to be extraordinarily robust under ultrashort, pulsed laser light conditions with a significant amount of excitation energy, maintaining structural and chemical stability. The most effective fluorescence output was achieved through dye placement at optimized densities coupled to the exterior surface avoiding conjugated ring systems. Lifetime measurements indicate that fluorescence output depends not only on spacing the fluorophores, but also on dimer stacking and configurational changes leading to radiationless relaxation—and these processes are related to the conjugation chemistry and nanoparticle shape. For biological applications, the particles were also examined in tissue culture, from which it was found that the optical properties differed from those found on the benchtop due to effects from cellular processes and uptake kinetics. Data indicate that fluorescent cargos are released in the endolysosomal compartment of the cell targeted by the virus-based optical probes. These studies provide insight into the optical properties and fates of fluorescent proteinaceous imaging probes. The cellular release of cargo has implications not only for virus-based optical probes, but also for drug delivery and release systems.
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- 2015
12. Tobacco Mosaic Virus-Delivered Cisplatin Restores Efficacy in Platinum-Resistant Ovarian Cancer Cells
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Anna E. Czapar, Nicole F. Steinmetz, Ravi Patel, and Christina E. Franke
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0301 basic medicine ,endocrine system diseases ,viruses ,medicine.medical_treatment ,Chemistry, Pharmaceutical ,Cell ,Pharmaceutical Science ,Antineoplastic Agents ,02 engineering and technology ,Drug resistance ,Nanoconjugates ,Biology ,03 medical and health sciences ,Cell Line, Tumor ,Drug Discovery ,Tobacco mosaic virus ,medicine ,Humans ,DNA Breaks, Double-Stranded ,Cisplatin ,Ovarian Neoplasms ,Chemotherapy ,Dose-Response Relationship, Drug ,fungi ,021001 nanoscience & nanotechnology ,medicine.disease ,Virology ,Tobacco Mosaic Virus ,030104 developmental biology ,medicine.anatomical_structure ,Drug Resistance, Neoplasm ,Drug delivery ,Cancer research ,Molecular Medicine ,Click Chemistry ,Female ,Nanocarriers ,Drug Screening Assays, Antitumor ,0210 nano-technology ,Ovarian cancer ,medicine.drug - Abstract
Platinum resistance in ovarian cancer is the major determinant of disease prognosis. Resistance can first appear at the onset of disease or develop in response to platinum-based chemotherapy. Due to poor response to alternate chemotherapies and lack of targeted therapies, there is an urgent clinical need for a new avenue toward treatment of platinum-resistant (PR) ovarian cancer. Nanoscale delivery systems hold potential to overcome resistance mechanisms. In this work, we present tobacco mosaic virus (TMV) as a nanocarrier for cisplatin for treatment of PR ovarian cancer cells. The TMV-cisplatin conjugate (TMV-cisPt) was synthesized using a charge-driven reaction that, like a classic click reaction, is simple and reliable for large-scale production. Up to ∼1900 cisPt were loaded per TMV-cisPt with biphasic release profiles characterized by a fast half-life (t1) of ∼1 h and slow half-life (t2) of ∼12 h independent of pH. Efficient cell uptake of TMV was observed when incubated with ovarian cancer cells, an...
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- 2017
13. POxylation as an alternative stealth coating for biomedical applications
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Nicole F. Steinmetz, Rainer Jordan, Herdis Bludau, Anna E. Czapar, Sourabh Shukla, and Andrzej S. Pitek
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Materials science ,Polymers and Plastics ,General Physics and Astronomy ,Nanoparticle ,Nanotechnology ,02 engineering and technology ,Polyethylene glycol ,engineering.material ,010402 general chemistry ,01 natural sciences ,Article ,chemistry.chemical_compound ,Coating ,Materials Chemistry ,chemistry.chemical_classification ,Organic Chemistry ,Polymer ,021001 nanoscience & nanotechnology ,0104 chemical sciences ,chemistry ,Drug delivery ,engineering ,Nanomedicine ,Molecular imaging ,Nanocarriers ,0210 nano-technology - Abstract
Polyethylene glycol (PEG) polymers are currently used in a variety of medical formulations to reduce toxicity, minimize immune interactions and improve pharmacokinetics. Despite its widespread use however, the presence of anti-PEG antibodies indicates that this polymer has the potential to be immunogenic and antigenic. Here we present an alternative polymer, poly(2-oxazoline) (POx) for stealth applications, specifically shielding of a proteinaceous nanoparticle from recognition by the immune system. Tobacco mosaic virus (TMV) was used as our testbed due to its potential for use as a nanocarrier for drug delivery and molecular imaging applications.
- Published
- 2017
14. Optical and Magnetic Resonance Imaging Using Fluorous Colloidal Nanoparticles
- Author
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Anna E. Czapar, Nicole F. Steinmetz, Kristen S. Wek, Charlie Wang, Jonathan K. Pokorski, Jaqueline D. Wallat, Amy M. Wen, and Xin Yu
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Treatment response ,Materials science ,Polymers and Plastics ,Polymers ,Bioengineering ,Triple Negative Breast Neoplasms ,02 engineering and technology ,010402 general chemistry ,01 natural sciences ,Imaging phantom ,Article ,Biomaterials ,Fluorine-19 Magnetic Resonance Imaging ,Nuclear magnetic resonance ,Materials Chemistry ,medicine ,Humans ,Cells, Cultured ,Ovarian Neoplasms ,medicine.diagnostic_test ,Macrophages ,Disease progression ,Optical Imaging ,Magnetic resonance imaging ,Longitudinal imaging ,021001 nanoscience & nanotechnology ,Polymeric nanoparticles ,Fluorescence ,Xenograft Model Antitumor Assays ,0104 chemical sciences ,Colloidal nanoparticles ,Nanoparticles ,Female ,0210 nano-technology - Abstract
Improved imaging of cancerous tissue has the potential to aid prognosis and improve patient outcome through longitudinal imaging of treatment response and disease progression. While nuclear imaging has made headway in cancer imaging, fluorinated tracers that enable magnetic resonance imaging (19F MRI) hold promise, particularly for repeated imaging sessions because nonionizing radiation is used. Fluorine MRI detects molecular signatures by imaging a fluorinated tracer and takes advantage of the spatial and anatomical resolution afforded by MRI. This manuscript describes a fluorous polymeric nanoparticle that is capable of 19F MR imaging and fluorescent tracking for in vitro and in vivo monitoring of immune cells and cancerous tissue. The fluorous particle is derived from low-molecular-weight amphiphilic copolymers that self-assemble into micelles with a hydrodynamic diameter of 260 nm. The polymer is MR-active at concentrations as low as 2.1 mM in phantom imaging studies. The fluorinated particle demonstrated rapid uptake into immune cells for potential cell-tracking or delineation of the tumor microenvironment and showed negligible toxicity. Systemic administration indicates significant uptake into two tumor types, triple-negative breast cancer and ovarian cancer, with little accumulation in off-target tissue. These results indicate a robust platform imaging agent capable of immune cell tracking and systemic disease monitoring with exceptional uptake of the nanoparticle in multiple cancer models.
- Published
- 2016
15. Tobacco Mosaic Virus Delivery of Phenanthriplatin for Cancer therapy
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Stephen J. Lippard, Anna E. Czapar, Imogen A. Riddell, Yao-Rong Zheng, Sourabh Shukla, Samuel G. Awuah, and Nicole F. Steinmetz
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Organoplatinum Compounds ,Cell Survival ,viruses ,General Physics and Astronomy ,Mice, Nude ,Antineoplastic Agents ,Triple Negative Breast Neoplasms ,02 engineering and technology ,010402 general chemistry ,01 natural sciences ,Article ,chemistry.chemical_compound ,Drug Delivery Systems ,In vivo ,Cell Line, Tumor ,Tobacco mosaic virus ,medicine ,Potency ,Animals ,Humans ,General Materials Science ,Tissue Distribution ,Triple-negative breast cancer ,Cisplatin ,Mice, Inbred BALB C ,fungi ,General Engineering ,Phenanthriplatin ,Translation (biology) ,021001 nanoscience & nanotechnology ,Virology ,0104 chemical sciences ,Phenanthridines ,Tobacco Mosaic Virus ,chemistry ,Cancer cell ,Cancer research ,Heterografts ,0210 nano-technology ,medicine.drug - Abstract
Phenanthriplatin, cis-[Pt(NH3)2Cl(phenanthridine)](NO3), is a cationic monofunctional DNA-binding platinum(II) anticancer drug candidate with unusual potency and cellular response profiles. Its in vivo efficacy has not yet been demonstrated, highlighting the need for a delivery system. Here we report tobacco mosaic virus (TMV) as a delivery system for phenanthriplatin. TMV forms hollow nanotubes with a polyanionic interior surface; capitalizing on this native structure, we developed a one-step phenanthriplatin loading protocol. Phenanthriplatin release from the carrier is induced in acidic environments. This delivery system, designated PhenPt-TMV, exhibits matched efficacy in a cancer cell panel compared to free phenanthriplatin. In vivo tumor delivery and efficacy were confirmed by using a mouse model of triple negative breast cancer. Tumors treated with PhenPt-TMV were 4× smaller than tumors treated with free phenanthriplatin or cisplatin, owing to increased accumulation of phenanthriplatin within the tumor tissue. The biology-derived TMV delivery system may facilitate translation of phenanthriplatin into the clinic.
- Published
- 2016
16. Paving the Way Toward Translational Application of Virus-Based Nanoparticles (VNPs): Preclinical Evaluation of Their Biological Fates
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Anna E. Czapar and Nicole F. Steinmetz
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Biodistribution ,Immune system ,biology ,Plant virus ,Cowpea mosaic virus ,Drug delivery ,Tobacco mosaic virus ,Potato virus X ,biology.organism_classification ,Virology ,Virus - Published
- 2016
17. Ion and solute transport by Prestin in Drosophila and Anopheles
- Author
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Michael F. Romero, Anna E. Czapar, Lauren R Brin, Pablo Cabrero, Paul J. Linser, Alyona Haritonova, James R. Thompson, Daniel P. Bondeson, Taku Hirata, and Julian A. T. Dow
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Malpighian tubule system ,Physiology ,Xenopus ,Protein Serine-Threonine Kinases ,Article ,Anopheles ,Genetic model ,SLC26A6 ,Animals ,Drosophila Proteins ,Chloride-Bicarbonate Antiporters ,Prestin ,Phylogeny ,Ion transporter ,Ion Transport ,Water transport ,biology ,fungi ,biology.organism_classification ,Biochemistry ,Insect Science ,biology.protein ,Drosophila ,Drosophila melanogaster ,Drosophila Protein ,Signal Transduction - Abstract
The gut and Malpighian tubules of insects are the primary sites of active solute and water transport for controlling hemolymph and urine composition, pH, and osmolarity. These processes depend on ATPase (pumps), channels and solute carriers (Slc proteins). Maturation of genomic databases enables us to identify the putative molecular players for these processes. Anion transporters of the Slc4 family, AE1 and NDAE1, have been reported as HCO(3)(-) transporters, but are only part of the story. Here we report Dipteran (Drosophila melanogaster (d) and Anopheles gambiae (Ag)) anion exchangers, belonging to the Slc26 family, which are multi-functional anion exchangers. One Drosophila and two Ag homologues of mammalian Slc26a5 (Prestin) and Slc26a6 (aka, PAT1, CFEX) were identified and designated dPrestin, AgPrestinA and AgPrestinB. dPrestin and AgPrestinB show electrogenic anion exchange (Cl(-)/nHCO(3)(-), Cl(-)/SO(4)(2-) and Cl(-)/oxalate(2-)) in an oocyte expression system. Since these transporters are the only Dipteran Slc26 proteins whose transport is similar to mammalian Slc26a6, we submit that Dipteran Prestin are functional and even molecular orthologues of mammalian Slc26a6. OSR1 kinase increases dPrestin ion transport, implying another set of physiological processes controlled by WNK/SPAK signaling in epithelia. All of these mRNAs are highly expressed in the gut and Malpighian tubules. Dipteran Prestin proteins appear suited for central roles in bicarbonate, sulfate and oxalate metabolism including generating the high pH conditions measured in the Dipteran midgut lumen. Finally, we present and discuss Drosophila genetic models that integrate these processes.
- Published
- 2012
18. Interface of Physics and Biology: Engineering Virus-Based Nanoparticles for Biophotonics.
- Author
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Amy M. Wen, Melissa Infusino, Antonio De Luca, DanielL. Kernan, Anna E. Czapar, Giuseppe Strangi, and Nicole F. Steinmetz
- Published
- 2015
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