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Article ; Online: Nanoscale flow cytometry to distinguish subpopulations of prostate extracellular vesicles in patient plasma.

Padda, Ranjit S / Deng, Florence K / Brett, Sabine I / Biggs, Colleen N / Durfee, Paul N / Brinker, Charles J / Williams, Karla C / Leong, Hon S

The Prostate

2019 Volume 79, Issue 6, Page(s) 592–603

Abstract: Objective: To determine if prostate-derived extracellular vesicles (EVs) present in patient plasma samples are of exocytotic origin (exosomes) or released by the cell membrane (microparticles/microvesicles). Both malignant and normal prostate cells ... ...

Abstract	Objective: To determine if prostate-derived extracellular vesicles (EVs) present in patient plasma samples are of exocytotic origin (exosomes) or released by the cell membrane (microparticles/microvesicles). Both malignant and normal prostate cells release two types of EVs into the circulation, exosomes, and microparticles/microvesicles which differ in size, origin, and mode of release. Determining what proportion of prostate-derived EVs are of exosomal versus microparticle/microvesicle EV subtype is of potential diagnostic significance. Materials and methods: Multi-parametric analytical platforms such as nanoscale flow cytometry (nFC) were used to analyze prostate derived extracellular vesicles. Plasmas from prostate cancer (PCa) patient plasmas representing benign prostatic hyperplasia (BPH), low grade prostate cancer (Gleason Score 3 + 3) and high grade prostate cancer (Gleason Score ≥4 + 4) were analyzed for various exosome markers (CD9, CD63, CD81) and a prostate specific tissue marker (prostate specific membrane antigen/PSMA). Results: By using nanoscale flow cytometry, we determine that prostate derived EVs are primarily of cell membrane origin, microparticles/microvesicles, and not all PSMA expressing EVs co-express exosomal markers such as CD9, CD63, and CD81. CD9 was the most abundant exosomal marker on prostate derived EVs (12-19%). There was no trend observed in terms of more PSMA + CD9 or PSMA + CD63 co-expressing EVs versus increasing grade of prostate cancer. Conclusion: The majority of prostate derived EVs present in plasmas are from the cell membrane as evidenced by their size and most importantly, lack of co-expression of exosomal markers such as CD9/CD63/CD81. In fact, CD81 was not present on any prostate derived EVs in patient plasmas whereas CD9 was present on a minority of prostate derived EVs. The addition of an exosomal marker for detection of prostate-derived EVs does not provide greater clarity in distinguishing EVs released by the prostate.
MeSH term(s)	Biomarkers/metabolism ; Cell-Derived Microparticles/metabolism ; Cell-Derived Microparticles/pathology ; Exosomes/metabolism ; Exosomes/pathology ; Extracellular Vesicles/classification ; Extracellular Vesicles/pathology ; Flow Cytometry/methods ; Humans ; Male ; Nanotechnology/methods ; Neoplasm Grading ; Prostate/metabolism ; Prostate/pathology ; Prostatic Hyperplasia/blood ; Prostatic Hyperplasia/pathology ; Prostatic Neoplasms/blood ; Prostatic Neoplasms/pathology ; Tetraspanin 29/analysis ; Tetraspanin 30/analysis
Chemical Substances	Biomarkers ; Tetraspanin 29 ; Tetraspanin 30
Language	English
Publishing date	2019-01-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	604707-5
ISSN	1097-0045 ; 0270-4137
ISSN (online)	1097-0045
ISSN	0270-4137
DOI	10.1002/pros.23764
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Article ; Online: The Use of an Integrated Website to Enhance the Educational Experience in a Medical School Radiology Clerkship Course.

Desai, Naman S / Bunch, Paul M / DiSalvo, Donald N / O'Brien, Reiko / Andriole, Katherine P / Smith, Terri / Durfee, Sara M

Current problems in diagnostic radiology

2016 Volume 45, Issue 1, Page(s) 17–22

Abstract: The purpose of this study was to demonstrate the feasibility of creating an integrated website for the medical students enrolled in a core radiology clerkship and to assess the impact of this website on students' overall educational experience. An ... ...

Abstract	The purpose of this study was to demonstrate the feasibility of creating an integrated website for the medical students enrolled in a core radiology clerkship and to assess the impact of this website on students' overall educational experience. An integrated website was created for the medical students and hosted on the main departmental website. The components of the website included: announcements and password-protected schedule, curriculum, student assessment, information about different radiology sections, digital resources, and fourth year opportunities. The schedule section was created using Google Calendar to facilitate automatic syncing and real-time updates to the students' mobile devices. Weblinks for resources and assignments were incorporated into the calendar entries, which could be "pushed" to students in real time. Student attitudes were assessed via an exit survey. Various website usage statistics were collected. A total of 35 students who have rotated through the month-long clerkship thus far have used the website. Overall, 80% of students accessed the website once or multiple times a day. Over 90% of students thought that the website was well organized and easy to use; having access to the schedule on a smartphone had a positive impact on overall clerkship experience; the website had an overall positive impact on their clerkship experience; and they would recommend it to visiting medical students. Since July 2013, there have been a total of 9740 page views with 4113 unique visits to the website (an average of 17 visits per day from 6 visitors per day). The authors conclude that the creation of an integrated website has a positive impact on students' overall educational experience.
MeSH term(s)	Clinical Clerkship/methods ; Curriculum ; Feasibility Studies ; Humans ; Internet ; Radiology/education ; Schools, Medical ; Students, Medical
Language	English
Publishing date	2016-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	198954-6
ISSN	1535-6302 ; 0363-0188
ISSN (online)	1535-6302
ISSN	0363-0188
DOI	10.1067/j.cpradiol.2015.03.002
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Article ; Online: Protocells: Modular Mesoporous Silica Nanoparticle-Supported Lipid Bilayers for Drug Delivery.

Butler, Kimberly S / Durfee, Paul N / Theron, Christophe / Ashley, Carlee E / Carnes, Eric C / Brinker, C Jeffrey

Small (Weinheim an der Bergstrasse, Germany)

2016 Volume 12, Issue 16, Page(s) 2173–2185

Abstract: Mesoporous silica nanoparticle-supported lipid bilayers, termed 'protocells,' represent a potentially transformative class of therapeutic and theranostic delivery vehicle. The field of targeted drug delivery poses considerable challenges that cannot be ... ...

Abstract	Mesoporous silica nanoparticle-supported lipid bilayers, termed 'protocells,' represent a potentially transformative class of therapeutic and theranostic delivery vehicle. The field of targeted drug delivery poses considerable challenges that cannot be addressed with a single 'magic bullet'. Consequently, the protocell has been designed as a modular platform composed of interchangeable biocompatible components. The mesoporous silica core has variable size and shape to direct biodistribution and a controlled pore size and surface chemistry to accommodate diverse cargo. The encapsulating supported lipid bilayer can be modified with targeting and trafficking ligands as well as polyethylene glycol (PEG) to effect selective binding, endosomal escape of cargo, drug efflux prevention, and potent therapeutic delivery, while maintaining in vivo colloidal stability. This review describes the individual components of the platform, including the mesoporous silica nanoparticle core and supported lipid bilayer, their assembly (by multiple techniques) into a protocell, and the combined, often synergistic, performance of the protocell based on in vitro and in vivo studies, including the assessment of biocompatibility and toxicity. In closing, the many emerging variations of the protocell theme and the future directions for protocell research are commented on.
MeSH term(s)	Animals ; Biocompatible Materials/chemistry ; Cell Line ; Colloids/chemistry ; Drug Delivery Systems ; Humans ; Ligands ; Lipid Bilayers/chemistry ; Liposomes/chemistry ; Nanomedicine/methods ; Nanoparticles/chemistry ; Nanostructures/chemistry ; Neoplasms/drug therapy ; Peptides/chemistry ; Polyethylene Glycols/chemistry ; Porosity ; RNA, Small Interfering/chemistry ; Silicon Dioxide/chemistry ; Tissue Distribution ; Tumor Microenvironment
Chemical Substances	Biocompatible Materials ; Colloids ; Ligands ; Lipid Bilayers ; Liposomes ; Peptides ; RNA, Small Interfering ; Polyethylene Glycols (3WJQ0SDW1A) ; Silicon Dioxide (7631-86-9)
Language	English
Publishing date	2016-01-18
Publishing country	Germany
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ZDB-ID	2168935-0
ISSN	1613-6829 ; 1613-6810
ISSN (online)	1613-6829
ISSN	1613-6810
DOI	10.1002/smll.201502119
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Article ; Online: Understanding the Connection between Nanoparticle Uptake and Cancer Treatment Efficacy using Mathematical Modeling.

Brocato, Terisse A / Coker, Eric N / Durfee, Paul N / Lin, Yu-Shen / Townson, Jason / Wyckoff, Edward F / Cristini, Vittorio / Brinker, C Jeffrey / Wang, Zhihui

Scientific reports

2018 Volume 8, Issue 1, Page(s) 7538

Abstract: Nanoparticles have shown great promise in improving cancer treatment efficacy while reducing toxicity and treatment side effects. Predicting the treatment outcome for nanoparticle systems by measuring nanoparticle biodistribution has been challenging due ...

Abstract	Nanoparticles have shown great promise in improving cancer treatment efficacy while reducing toxicity and treatment side effects. Predicting the treatment outcome for nanoparticle systems by measuring nanoparticle biodistribution has been challenging due to the commonly unmatched, heterogeneous distribution of nanoparticles relative to free drug distribution. We here present a proof-of-concept study that uses mathematical modeling together with experimentation to address this challenge. Individual mice with 4T1 breast cancer were treated with either nanoparticle-delivered or free doxorubicin, with results demonstrating improved cancer kill efficacy of doxorubicin loaded nanoparticles in comparison to free doxorubicin. We then developed a mathematical theory to render model predictions from measured nanoparticle biodistribution, as determined using graphite furnace atomic absorption. Model analysis finds that treatment efficacy increased exponentially with increased nanoparticle accumulation within the tumor, emphasizing the significance of developing new ways to optimize the delivery efficiency of nanoparticles to the tumor microenvironment.
MeSH term(s)	Animals ; Biological Availability ; Breast Neoplasms/drug therapy ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Cell Line, Tumor ; Doxorubicin/administration & dosage ; Doxorubicin/pharmacokinetics ; Drug Delivery Systems ; Female ; Humans ; Mice ; Mice, Inbred BALB C ; Models, Theoretical ; Nanoparticles/administration & dosage ; Neoplasms/drug therapy ; Neoplasms/metabolism ; Neoplasms/pathology ; Pharmacokinetics ; Tissue Distribution ; Tumor Burden ; Xenograft Model Antitumor Assays
Chemical Substances	Doxorubicin (80168379AG)
Language	English
Publishing date	2018-05-24
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-018-25878-8
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Article ; Online: Establishing the effects of mesoporous silica nanoparticle properties on in vivo disposition using imaging-based pharmacokinetics.

Dogra, Prashant / Adolphi, Natalie L / Wang, Zhihui / Lin, Yu-Shen / Butler, Kimberly S / Durfee, Paul N / Croissant, Jonas G / Noureddine, Achraf / Coker, Eric N / Bearer, Elaine L / Cristini, Vittorio / Brinker, C Jeffrey

Nature communications

2018 Volume 9, Issue 1, Page(s) 4551

Abstract: The progress of nanoparticle (NP)-based drug delivery has been hindered by an inability to establish structure-activity relationships in vivo. Here, using stable, monosized, radiolabeled, mesoporous silica nanoparticles (MSNs), we apply an integrated ... ...

Abstract	The progress of nanoparticle (NP)-based drug delivery has been hindered by an inability to establish structure-activity relationships in vivo. Here, using stable, monosized, radiolabeled, mesoporous silica nanoparticles (MSNs), we apply an integrated SPECT/CT imaging and mathematical modeling approach to understand the combined effects of MSN size, surface chemistry and routes of administration on biodistribution and clearance kinetics in healthy rats. We show that increased particle size from ~32- to ~142-nm results in a monotonic decrease in systemic bioavailability, irrespective of route of administration, with corresponding accumulation in liver and spleen. Cationic MSNs with surface exposed amines (PEI) have reduced circulation, compared to MSNs of identical size and charge but with shielded amines (QA), due to rapid sequestration into liver and spleen. However, QA show greater total excretion than PEI and their size-matched neutral counterparts (TMS). Overall, we provide important predictive functional correlations to support the rational design of nanomedicines.
MeSH term(s)	Animals ; Female ; Half-Life ; Kinetics ; Nanoparticles/chemistry ; Particle Size ; Porosity ; Rats, Inbred F344 ; Silicon Dioxide/chemistry ; Silicon Dioxide/pharmacokinetics ; Static Electricity ; Tissue Distribution ; Tomography, Emission-Computed, Single-Photon ; Tomography, X-Ray Computed
Chemical Substances	Silicon Dioxide (7631-86-9)
Language	English
Publishing date	2018-10-31
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-018-06730-z
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Article ; Online: A novel approach for targeted delivery to motoneurons using cholera toxin-B modified protocells.

Gonzalez Porras, Maria A / Durfee, Paul N / Gregory, Ashley M / Sieck, Gary C / Brinker, C Jeffrey / Mantilla, Carlos B

Journal of neuroscience methods

2016 Volume 273, Page(s) 160–174

Abstract: Background: Trophic interactions between muscle fibers and motoneurons at the neuromuscular junction (NMJ) play a critical role in determining motor function throughout development, ageing, injury, or disease. Treatment of neuromuscular disorders is ... ...

Abstract	Background: Trophic interactions between muscle fibers and motoneurons at the neuromuscular junction (NMJ) play a critical role in determining motor function throughout development, ageing, injury, or disease. Treatment of neuromuscular disorders is hindered by the inability to selectively target motoneurons with pharmacological and genetic interventions. New method: We describe a novel delivery system to motoneurons using mesoporous silica nanoparticles encapsulated within a lipid bilayer (protocells) and modified with the atoxic subunit B of the cholera toxin (CTB) that binds to gangliosides present on neuronal membranes. Results: CTB modified protocells showed significantly greater motoneuron uptake compared to unmodified protocells after 24h of treatment (60% vs. 15%, respectively). CTB-protocells showed specific uptake by motoneurons compared to muscle cells and demonstrated cargo release of a surrogate drug. Protocells showed a lack of cytotoxicity and unimpaired cellular proliferation. In isolated diaphragm muscle-phrenic nerve preparations, preferential axon terminal uptake of CTB-modified protocells was observed compared to uptake in surrounding muscle tissue. A larger proportion of axon terminals displayed uptake following treatment with CTB-protocells compared to unmodified protocells (40% vs. 6%, respectively). Comparison with existing method(s): Current motoneuron targeting strategies lack the functionality to load and deliver multiple cargos. CTB-protocells capitalizes on the advantages of liposomes and mesoporous silica nanoparticles allowing a large loading capacity and cargo release. The ability of CTB-protocells to target motoneurons at the NMJ confers a great advantage over existing methods. Conclusions: CTB-protocells constitute a viable targeted motoneuron delivery system for drugs and genes facilitating various therapies for neuromuscular diseases.
MeSH term(s)	Animals ; Artificial Cells/metabolism ; Artificial Cells/ultrastructure ; Benzoxazoles/metabolism ; Cells, Cultured ; Chemical Phenomena ; Cholera Toxin/administration & dosage ; Cholera Toxin/metabolism ; Cholera Toxin/pharmacology ; Diaphragm/cytology ; Drug Delivery Systems/methods ; In Vitro Techniques ; Lipid Bilayers/metabolism ; Male ; Motor Neurons/drug effects ; Motor Neurons/metabolism ; Motor Neurons/ultrastructure ; Neuromuscular Junction/metabolism ; Neuromuscular Junction/ultrastructure ; Presynaptic Terminals/metabolism ; Quinolinium Compounds/metabolism ; Rats ; Silicon Dioxide ; Time Factors
Chemical Substances	Benzoxazoles ; Lipid Bilayers ; Quinolinium Compounds ; YO-PRO 1 (152068-09-2) ; Silicon Dioxide (7631-86-9) ; Cholera Toxin (9012-63-9)
Language	English
Publishing date	2016-09-15
Publishing country	Netherlands
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't
ZDB-ID	282721-9
ISSN	1872-678X ; 0165-0270
ISSN (online)	1872-678X
ISSN	0165-0270
DOI	10.1016/j.jneumeth.2016.09.003
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Article ; Online: Isometric skeletal muscle force measurement in primary myopathies.

Ginz, Hans F / Iaizzo, Paul A / Schweikert, Kathi / Durfee, William K

Muscle & nerve

2016 Volume 53, Issue 6, Page(s) 913–917

Abstract: ... for nonvoluntary force assessment.: Methods: We tested 8 patients (unknown myopathy n = 2, inflammatory myopathy ... n = 1 each). Isometric twitch torques of ankle dorsiflexors were measured after fibular nerve ...

Abstract	Introduction: In myopathy patients, it is useful to measure skeletal muscle forces. Conventional methods require voluntary muscle activation, which can be unreliable. We evaluated a device for nonvoluntary force assessment. Methods: We tested 8 patients (unknown myopathy n = 2, inflammatory myopathy, facioscapulohumeral muscular dystrophy, mitochondrial myopathy, dysferlinopathy, multi-minicore disease, Becker-Kiener muscular dystrophy, n = 1 each). Isometric twitch torques of ankle dorsiflexors were measured after fibular nerve stimulation. Results: Six patients had decreased torques vs. 8 controls (men: median Newton-meter 1.6 vs. 5.7, women: 0.2 vs. 3.9, both P < 0.0001). Values correlated with Manual Muscle Test results (r = 0.73; r(2) = 0.53; P < 0.0001). In weak dorsiflexors, torque could be measured despite lower signal-to-noise ratios. In 2 patients with hypertrophy, we measured increased torques. Conclusions: Nonvoluntary muscle force assessment can be used in patients with myopathies, and values correlate with voluntary forces determined by traditional methods. Muscle Nerve 53: 913-917, 2016.
MeSH term(s)	Adult ; Ankle Joint/innervation ; Electric Stimulation ; Electromyography ; Female ; Humans ; Isometric Contraction/physiology ; Male ; Middle Aged ; Muscle, Skeletal/physiopathology ; Muscular Diseases/pathology ; Muscular Diseases/physiopathology ; Statistics as Topic ; Statistics, Nonparametric ; Switzerland ; Torque
Language	English
Publishing date	2016
Publishing country	United States
Document type	Journal Article
ZDB-ID	438353-9
ISSN	1097-4598 ; 0148-639X
ISSN (online)	1097-4598
ISSN	0148-639X
DOI	10.1002/mus.24954
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Zs.A 1449: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Establishing the effects of mesoporous silica nanoparticle properties on in vivo disposition using imaging-based pharmacokinetics

Prashant Dogra / Natalie L. Adolphi / Zhihui Wang / Yu-Shen Lin / Kimberly S. Butler / Paul N. Durfee / Jonas G. Croissant / Achraf Noureddine / Eric N. Coker / Elaine L. Bearer / Vittorio Cristini / C. Jeffrey Brinker

Nature Communications, Vol 9, Iss 1, Pp 1-

2018 Volume 14

Abstract: Nanoparticle applications are limited by insufficient understanding of physiochemical properties on in vivo disposition. Here, the authors explore the influence of size, surface chemistry and administration on the biodisposition of mesoporous silica ... ...

Abstract	Nanoparticle applications are limited by insufficient understanding of physiochemical properties on in vivo disposition. Here, the authors explore the influence of size, surface chemistry and administration on the biodisposition of mesoporous silica nanoparticles using image-based pharmacokinetics.
Keywords	Science ; Q
Language	English
Publishing date	2018-10-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Establishing the effects of mesoporous silica nanoparticle properties on in vivo disposition using imaging-based pharmacokinetics

Nature Communications, Vol 9, Iss 1, Pp 1-

2018 Volume 14

Abstract	Nanoparticle applications are limited by insufficient understanding of physiochemical properties on in vivo disposition. Here, the authors explore the influence of size, surface chemistry and administration on the biodisposition of mesoporous silica nanoparticles using image-based pharmacokinetics.
Keywords	Science ; Q
Language	English
Publishing date	2018-10-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Understanding the Connection between Nanoparticle Uptake and Cancer Treatment Efficacy using Mathematical Modeling

Terisse A. Brocato / Eric N. Coker / Paul N. Durfee / Yu-Shen Lin / Jason Townson / Edward F. Wyckoff / Vittorio Cristini / C. Jeffrey Brinker / Zhihui Wang

Scientific Reports, Vol 8, Iss 1, Pp 1-

2018 Volume 8

Abstract: Abstract Nanoparticles have shown great promise in improving cancer treatment efficacy while reducing toxicity and treatment side effects. Predicting the treatment outcome for nanoparticle systems by measuring nanoparticle biodistribution has been ... ...

Abstract	Abstract Nanoparticles have shown great promise in improving cancer treatment efficacy while reducing toxicity and treatment side effects. Predicting the treatment outcome for nanoparticle systems by measuring nanoparticle biodistribution has been challenging due to the commonly unmatched, heterogeneous distribution of nanoparticles relative to free drug distribution. We here present a proof-of-concept study that uses mathematical modeling together with experimentation to address this challenge. Individual mice with 4T1 breast cancer were treated with either nanoparticle-delivered or free doxorubicin, with results demonstrating improved cancer kill efficacy of doxorubicin loaded nanoparticles in comparison to free doxorubicin. We then developed a mathematical theory to render model predictions from measured nanoparticle biodistribution, as determined using graphite furnace atomic absorption. Model analysis finds that treatment efficacy increased exponentially with increased nanoparticle accumulation within the tumor, emphasizing the significance of developing new ways to optimize the delivery efficiency of nanoparticles to the tumor microenvironment.
Keywords	Medicine ; R ; Science ; Q
Subject code	000
Language	English
Publishing date	2018-05-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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