Publications by authors named "Alexis Carpenter"

19 Publications

  • Page 1 of 1

Infection of mosquitoes with midgut-attenuated Sindbis virus reduces, but does not eliminate, disseminated infection.

J Virol 2021 Apr 14. Epub 2021 Apr 14.

Division of Biology, Kansas State University, Manhattan, Kansas 66503

Arboviruses are transmitted by specific vectors and the reasons for this specificity are not fully understood. One contributing factor is the existence of tissue barriers within the vector such as the midgut escape barrier. We used miRNA targeting of Sindbis virus (SINV) to study how replication in midgut cells contributes to overcoming this barrier in the mosquito SINV constructs were designed to be attenuated specifically in midgut cells by inserting binding sites for midgut-specific miRNAs into either the 3' untranslated region (MRE3'miRT) or the structural open reading frame (MRE-ORFmiRT) of the SINV genome. Both miRNA-targeted viruses replicated less efficiently than control viruses in the presence of these miRNAs. When mosquitoes were given infectious blood meals containing miRNA-targeted viruses, only around 20% (MRE3'miRT) or 40% (MRE-ORFmiRT) of mosquitoes developed disseminated infection. In contrast, dissemination occurred in almost all mosquitoes fed control viruses. Deep sequencing of virus populations from individual mosquitoes ruled out selection for mutations in the inserted target sequences as being the cause for dissemination in these mosquitoes. In mosquitoes that became infected with miRNA-targeted viruses, titers were equivalent to control virus in both the midgut and the carcass and there was no evidence of a threshold titer necessary for dissemination. Instead, it appeared that if infection was successfully established in the midgut, replication and dissemination were largely normal. Our results support the hypothesis that replication is an important factor in allowing SINV to overcome the midgut escape barrier, but hint that other factors are also likely involved.When a mosquito ingests an arbovirus during a blood meal, the arbovirus must escape from the midgut of the vector and infect the salivary glands in order to be transmitted to a new host. We used tissue-specific miRNA targeting to examine the requirement for Sindbis virus (SINV) to replicate in midgut epithelium in order to cause disseminated infection in the mosquito Our results indicate that specifically reducing the ability of SINV to replicate in the mosquito midgut reduces its overall ability to establish infection in the mosquito, but if infection is established, replication and dissemination occur normally. These results are consistent with an importance for replication in the midgut epithelium in aiding arboviruses in crossing the midgut barrier.
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http://dx.doi.org/10.1128/JVI.00136-21DOI Listing
April 2021

Reinstatement of item-specific contextual details during retrieval supports recombination-related false memories.

Neuroimage 2021 Apr 6;236:118033. Epub 2021 Apr 6.

Department of Psychology and Center for Brain Science, Harvard University, 33 Kirkland Street, Cambridge, MA 02138, United States.

Flexible retrieval mechanisms that allow us to infer relationships across events may also lead to memory errors or distortion when details of one event are misattributed to the related event. Here, we tested how making successful inferences alters representation of overlapping events, leading to false memories. Participants encoded overlapping associations ('AB' and 'BC'), each of which was superimposed on different indoor and outdoor scenes that were pre-exposed prior to associative learning. Participants were subsequently tested on both the directly learned pairs ('AB' and 'BC') and inferred relationships across pairs ('AC'). We predicted that when people make a correct inference, features associated with overlapping events may become integrated in memory. To test this hypothesis, participants completed a final detailed retrieval test, in which they had to recall the scene associated with initially learned 'AB' pairs (or 'BC' pairs). We found that the outcome of inference decisions impacted the degree to which neural patterns elicited during detailed 'AB' retrieval reflected reinstatement of the scene associated with the overlapping 'BC' event. After successful inference, neural patterns in the anterior hippocampus, posterior medial prefrontal cortex, and our content-reinstatement region (left inferior temporal gyrus) were more similar to the overlapping, yet incorrect 'BC' context relative to after unsuccessful inference. Further, greater hippocampal activity during inference was associated with greater reinstatement of the incorrect, overlapping context in our content-reinstatement region, which in turn tracked contextual misattributions during detailed retrieval. These results suggest recombining memories during successful inference can lead to misattribution of contextual details across related events, resulting in false memories.
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http://dx.doi.org/10.1016/j.neuroimage.2021.118033DOI Listing
April 2021

Cellulose nanocrystal zero-valent iron nanocomposites for groundwater remediation.

Environ Sci Nano 2017 Jun 7;6(6):1294-1303. Epub 2017 Apr 7.

Civil and Environmental Engineering, Duke University, 120 Hudson Hall, Durham, NC 27708-0287, USA.

Zero-valent iron nanoparticles (nano-ZVIs) have been widely studied for remediation of groundwater and other environmental matrices. Nano-ZVI particle mobility and reactivity are still the main impediments in achieving efficient groundwater remediation. Compared to the nano-ZVI "coating" strategy, nano-ZVI stabilization on supporting material allows direct contact with the contaminant, reduces the electron path from the nano-ZVI to the target contaminant and increases nano-ZVI reactivity. Herein, we report the synthesis of nano-ZVI stabilized by cellulose nanocrystal (CNC) rigid nanomaterials (CNC-nano-ZVI; Fe/CNC = 1 w/w) with two different CNC functional surfaces (-OH and -COOH) using a classic sodium borohydride synthesis pathway. The final nanocomposites were thoroughly characterized and the reactivity of CNC-nano-ZVIs was assessed by their methyl orange (MO) dye degradation potential. The mobility of nanocomposites was determined in (sand/glass bead) porous media by utilizing a series of flowthrough transport column experiments. The synthesized CNC-nano-ZVI provided a stable colloidal suspension and demonstrated high mobility in porous media with an attachment efficiency () value of less than 0.23. In addition, reactivity toward MO increased up to 25% compared to bare ZVI. The use of CNC as a delivery vehicle shows promising potential to further improve the capability and applicability of nano-ZVI for groundwater remediation and can spur advancements in CNC-based nanocomposites for their application in environmental remediation.
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http://dx.doi.org/10.1039/c6en00572aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5929147PMC
June 2017

Flexible retrieval mechanisms supporting successful inference produce false memories in younger but not older adults.

Psychol Aging 2018 02;33(1):134-143

Department of Psychology, Harvard University.

Episodic memory involves flexible retrieval processes that allow a person to link elements of distinct episodes in order to make novel inferences across events. In younger adults, we recently found that the same retrieval-related recombination mechanism that supports successful associative inference produces source misattributions as a consequence of erroneous binding of contextual elements from distinct episodes. In the current experiment, we found that older adults, in contrast to younger adults, did not show an increase in source misattributions following successful associative inference. We observed this pattern both when (a) younger and older adults were tested under identical experimental conditions and (b) younger and older adults were matched on associative inference accuracy and overall source memory errors. We suggest that the differing patterns of results are a consequence of age-related deficits in associative binding during successful inferential retrieval. (PsycINFO Database Record
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http://dx.doi.org/10.1037/pag0000210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5836313PMC
February 2018

False memories, false preferences: Flexible retrieval mechanisms supporting successful inference bias novel decisions.

J Exp Psychol Gen 2018 07 8;147(7):988-1004. Epub 2018 Feb 8.

Department of Psychology and Center for Brain Science, Harvard University.

Prior research suggests that episodic memory can guide value-based decisions when single episodes are encoded in relation to the specific reward-context in which they were experienced. The current experiments examine the role that a flexible recombination-related retrieval mechanism that allows one to link together distinct events plays in the misattribution of specific reward-contexts across distinct episodes. To determine whether the same recombination-related retrieval mechanism supports both successful inference and transfer of reward-context across episodes, we developed a modified version of an associative inference paradigm in which participants encoded overlapping associations (AB, BC) that could later be linked to support inferential retrieval (AC), where one element ("A") was tied to reward. Our key experimental manipulation concerned whether value memory (Experiments 1 and 2) or decision bias tests (Experiment 3) were probed before or after the associative inference test, thereby allowing us to assess whether false value transfer and decision bias scores increased after as compared to before successful versus unsuccessful inference. Results revealed that participants more frequently misattributed the specific reward-context ("A") to unrewarded items ("C;" Experiments 1 and 2) and showed higher decision bias scores when asked to choose between two previously unrewarded items ("C;" Experiment 3) for successful compared with unsuccessful inference, but only when the value memory and decision bias tests were given after the associative inference test. These results suggest that a recombination-related retrieval mechanism that supports successful inference also contributes to the misattribution of reward-context in memory and further biases participants' novel value-based decisions. (PsycINFO Database Record
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http://dx.doi.org/10.1037/xge0000391DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6033641PMC
July 2018

Constructive episodic simulation, flexible recombination, and memory errors.

Behav Brain Sci 2018 01;41:e32

School of Psychology and Centre for Brain Research,University of Auckland,Auckland,New

According to Mahr & Csibra (M&C), the view that the constructive nature of episodic memory is related to its role in simulating future events has difficulty explaining why memory is often accurate. We hold this view, but disagree with their conclusion. Here we consider ideas and evidence regarding flexible recombination processes in episodic retrieval that accommodate both accuracy and distortion.
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http://dx.doi.org/10.1017/S0140525X17001510DOI Listing
January 2018

Remembering and imagining alternative versions of the personal past.

Neuropsychologia 2018 02 17;110:170-179. Epub 2017 Jun 17.

Department of Psychology, Harvard University, Cambridge 02138, USA; Center for Brain Science, Harvard University, Cambridge 02138, USA.

Although autobiographical memory and episodic simulations recruit similar core brain regions, episodic simulations engage additional neural recruitment in the frontoparietal control network due to greater demands on constructive processes. However, previous functional neuroimaging studies showing differences in remembering and episodic simulation have focused on veridical retrieval of past experiences, and thus have not fully considered how retrieving the past in different ways from how it was originally experienced may also place similar demands on constructive processes. Here we examined how alternative versions of the past are constructed when adopting different egocentric perspectives during autobiographical memory retrieval compared to simulating hypothetical events from the personal past that could have occurred, or episodic counterfactual thinking. Participants were asked to generate titles for specific autobiographical memories from the last five years, and then, during functional magnetic resonance (fMRI) scanning, were asked to repeatedly retrieve autobiographical memories or imagine counterfactual events cued by the titles. We used an fMRI adaptation paradigm in order to isolate neural regions that were sensitive to adopting alternative egocentric perspectives and counterfactual simulations of the personal past. The fMRI results revealed that voxels within left posterior inferior parietal and ventrolateral frontal cortices were sensitive to novel visual perspectives and counterfactual simulations. Our findings suggest that the neural regions supporting remembering become more similar to those underlying episodic simulation when we adopt alternative egocentric perspectives of the veridical past.
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http://dx.doi.org/10.1016/j.neuropsychologia.2017.06.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5733718PMC
February 2018

Flexible retrieval: When true inferences produce false memories.

J Exp Psychol Learn Mem Cogn 2017 03 5;43(3):335-349. Epub 2016 Dec 5.

Department of Psychology, Harvard University.

Episodic memory involves flexible retrieval processes that allow us to link together distinct episodes, make novel inferences across overlapping events, and recombine elements of past experiences when imagining future events. However, the same flexible retrieval and recombination processes that underpin these adaptive functions may also leave memory prone to error or distortion, such as source misattributions in which details of one event are mistakenly attributed to another related event. To determine whether the same recombination-related retrieval mechanism supports both successful inference and source memory errors, we developed a modified version of an associative inference paradigm in which participants encoded everyday scenes comprised of people, objects, and other contextual details. These scenes contained overlapping elements (AB, BC) that could later be linked to support novel inferential retrieval regarding elements that had not appeared together previously (AC). Our critical experimental manipulation concerned whether contextual details were probed or the associative inference test, thereby allowing us to assess whether (a) false memories increased for successful versus unsuccessful inferences, and (b) any such effects were specific to after compared with before participants received the inference test. In each of 4 experiments that used variants of this paradigm, participants were more susceptible to false memories for contextual details after successful than unsuccessful inferential retrieval, but only when contextual details were probed after the associative inference test. These results suggest that the retrieval-mediated recombination mechanism that underlies associative inference also contributes to source misattributions that result from combining elements of distinct episodes. (PsycINFO Database Record
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http://dx.doi.org/10.1037/xlm0000340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5334182PMC
March 2017

Are eyewitness accounts biased? Evaluating false memories for crimes involving in-group or out-group conflict.

Soc Neurosci 2018 02 17;13(1):74-93. Epub 2016 Nov 17.

b Department of Psychological & Brain Sciences , Indiana University , Bloomington , IN , USA.

Eyewitness testimony has been shown to be unreliable and susceptible to false memories. Whether eyewitness memory errors are influenced by the victim's group membership (relative to both the eyewitness and perpetrator) is underexplored. The current study used complementary behavioral and neuroimaging approaches to test the hypothesis that intragroup conflict heightens participants' susceptibility to subsequent false memories. Healthy young adults witnessed and later answered questions about events in which the perpetrator and victim were either 1) identified as in-group members relative to each other and the eyewitness, 2) out-group members relative to the eyewitness, but not each other, or 3) out-group members relative to each other (Experiments 1a and 1b). When perpetrators and victims were in-group members (intragroup conflict), participants showed heightened false memory rates. Moreover, false memories increased upon crime realization. Neuroimaging data analysis revealed that salient (as compared to ambiguous) intragroup conflict elicited heightened activation in neural regions associated with resolving cognitive conflict (anterior cingulate cortex; ACC). Increased functional connectivity between the ACC and dorsomedial prefrontal cortex was associated with subsequent false memories (Experiment 2). Results suggest that the social salience of the intragroup conflict may have been associated with participants' increased susceptibility to false memories.
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http://dx.doi.org/10.1080/17470919.2016.1253610DOI Listing
February 2018

Enhanced Biogas Production from Nanoscale Zero Valent Iron-Amended Anaerobic Bioreactors.

Environ Eng Sci 2015 Aug;32(8):647-655

Department of Civil and Environmental Engineering, Duke University , Durham, North Carolina. ; Center for the Environmental Implications of NanoTechnology, Duke University , Durham, North Carolina.

Addition of nanoscale zero valent iron (NZVI) to anaerobic batch reactors to enhance methanogenic activity is described. Two NZVI systems were tested: a commercially available NZVI (cNZVI) slurry and a freshly synthesized NZVI (sNZVI) suspension that was prepared immediately before addition to the reactors. In both systems, the addition of NZVI increased pH and decreased oxidation/reduction potential compared with unamended control reactors. Biodegradation of a model brewery wastewater was enhanced as indicated by an increase in chemical oxygen demand removal with both sNZVI and cNZVI amendments at all concentrations tested (1.25-5.0 g Fe/L). Methane production increased for all NZVI-amended bioreactors, with a maximum increase of 28% achieved on the addition of 2.5 and 5.0 g/L cNZVI. Addition of bulk zero-valent iron resulted in only a 5% increase in methane, indicating the advantage of using the nanoscale particles. NZVI amendments further improved produced biogas by decreasing the amount of CO released from the bioreactor by approximately 58%. Overall, addition of cNZVI proved more beneficial than the sNZVI at equal iron concentrations, due to decreased colloidal stability and larger effective particle size of sNZVI. Although some have reported cytotoxicity of NZVI to anaerobic microorganisms, work presented here suggests that NZVI of a certain particle size and reactivity can serve as an amendment to anaerobic digesters to enhance degradation and increase the value of the produced biogas, yielding a more energy-efficient anaerobic method for wastewater treatment.
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http://dx.doi.org/10.1089/ees.2014.0560DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4545702PMC
August 2015

Cellulose nanomaterials in water treatment technologies.

Environ Sci Technol 2015 May 15;49(9):5277-87. Epub 2015 Apr 15.

†Department of Civil and Environmental Engineering, Duke University, Durham, North Carolina 27708, United States.

Cellulose nanomaterials are naturally occurring with unique structural, mechanical and optical properties. While the paper and packaging, automotive, personal care, construction, and textiles industries have recognized cellulose nanomaterials' potential, we suggest cellulose nanomaterials have great untapped potential in water treatment technologies. In this review, we gather evidence of cellulose nanomaterials' beneficial role in environmental remediation and membranes for water filtration, including their high surface area-to-volume ratio, low environmental impact, high strength, functionalizability, and sustainability. We make direct comparison between cellulose nanomaterials and carbon nanotubes (CNTs) in terms of physical and chemical properties, production costs, use and disposal in order to show the potential of cellulose nanomaterials as a sustainable replacement for CNTs in water treatment technologies. Finally, we comment on the need for improved communication and collaboration across the myriad industries invested in cellulose nanomaterials production and development to achieve an efficient means to commercialization.
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http://dx.doi.org/10.1021/es506351rDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4544834PMC
May 2015

Role of size and shape on biofilm eradication for nitric oxide-releasing silica nanoparticles.

ACS Appl Mater Interfaces 2013 Oct 5;5(19):9322-9. Epub 2013 Sep 5.

Department of Chemistry, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina 27599, United States.

Nitric oxide (NO), a reactive free radical, has proven effective in eradicating bacterial biofilms with reduced risk of fostering antibacterial resistance. Herein, we evaluated the efficacy of NO-releasing silica nanoparticles against Gram-negative Pseudomonas aeruginosa and Gram-positive Staphylococcus aureus biofilms as a function of particle size and shape. Three sizes of NO-releasing silica nanoparticles (i.e., 14, 50, and 150 nm) with identical total NO release (∼0.3 μmol/mg) were utilized to study antibiofilm eradication as a function of size. To observe the role of particle shape on biofilm killing, we varied the aspect ratio of the NO-releasing silica particles from 1 to 8 while maintaining constant particle volume (∼0.02 μm(3)) and NO-release totals (∼0.7 μmol/mg). Nitric oxide-releasing particles with decreased size and increased aspect ratio were more effective against both P. aeruginosa and S. aureus biofilms, with the Gram-negative species exhibiting the greatest susceptibility to NO. To further understand the influence of these nanoparticle properties on NO-mediated antibacterial activity, we visualized intracellular NO concentrations and cell death with confocal microscopy. Smaller NO-releasing particles (14 nm) exhibited better NO delivery and enhanced bacteria killing compared to the larger (50 and 150 nm) particles. Likewise, the rod-like NO-releasing particles proved more effective than spherical particles in delivering NO and inducing greater antibacterial action throughout the biofilm.
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http://dx.doi.org/10.1021/am402618wDOI Listing
October 2013

-Protected Diazeniumdiolate-Modified Silica Nanoparticles for Extended Nitric Oxide Release from Dental Composites.

Biomater Sci 2013 May;1(5):456-459

Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA;

O-protected -diazeniumdiolate-based silanes were grafted onto mesoporous silica nanoparticles to yield a scaffold with an NO payload of 2.4 μmol NO/mg and NO release half-life of 23 d. Reduced (3-log) viable adhesion was observed for NO-releasing dental restorative materials modified with these particles relative to controls.
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http://dx.doi.org/10.1039/C3BM00153ADOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3733399PMC
May 2013

Nitric oxide-releasing silica nanoparticle-doped polyurethane electrospun fibers.

ACS Appl Mater Interfaces 2013 Aug 5;5(16):7956-64. Epub 2013 Aug 5.

Department of Chemistry, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.

Electrospun polyurethane fibers doped with nitric oxide (NO)-releasing silica particles are presented as novel macromolecular scaffolds with prolonged NO-release and high porosity. Fiber diameter (119-614 nm) and mechanical strength (1.7-34.5 MPa of modulus) were varied by altering polyurethane type and concentration, as well as the NO-releasing particle composition, size, and concentration. The resulting NO-releasing electrospun nanofibers exhibited ~83% porosity with flexible plastic or elastomeric behavior. The use of N-diazeniumdiolate- or S-nitrosothiol-modified particles yielded scaffolds exhibiting a wide range of NO release totals and durations (7.5 nmol mg(-1)-0.12 μmol mg(-1) and 7 h to 2 weeks, respectively). The application of NO-releasing porous materials as coatings for subcutaneous implants may improve tissue biocompatibility by mitigating the foreign body response and promoting cell integration.
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http://dx.doi.org/10.1021/am402044sDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3811043PMC
August 2013

Dual action antimicrobials: nitric oxide release from quaternary ammonium-functionalized silica nanoparticles.

Biomacromolecules 2012 Oct 21;13(10):3334-42. Epub 2012 Sep 21.

Department of Chemistry, University of North Carolina, Chapel Hill, NC 27599, USA.

The synthesis of quaternary ammonium (QA)-functionalized silica nanoparticles with and without nitric oxide (NO) release capabilities is described. Glycidyltrialkylammonium chlorides of varied alkyl chain lengths (i.e., methyl, butyl, octyl, and dodecyl) were tethered to the surface of amine-containing silica nanoparticles via a ring-opening reaction. Secondary amines throughout the particle were then functionalized with N-diazeniumdiolate NO donors to yield dual functional nanomaterials with surface QAs and total NO payloads of 0.3 μmol/mg. The bactericidal activities of singly (i.e., only NO-releasing or only QA-functionalized) and dual (i.e., NO-releasing and QA-functionalized) functional nanoparticles were tested against Gram-positive Staphylococcus aureus and Gram-negative Pseudomonas aeruginosa . Particles with only NO release capabilities alone were found to be more effective against P. aeruginosa , while particles with only QA-functionalities exhibited greater toxicity toward S. aureus . The minimum bactericidal concentrations (MBC) of QA-functionalized particles decreased with increasing alkyl chain length against both microbes tested. Combining NO release and QA-functionalities on the same particle resulted in an increase in bactericidal efficacy against S. aureus ; however, no change in activity against P. aeruginosa was observed compared to NO-releasing particles alone.
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http://dx.doi.org/10.1021/bm301108xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3482837PMC
October 2012

Nitric oxide release: part II. Therapeutic applications.

Chem Soc Rev 2012 May 24;41(10):3742-52. Epub 2012 Feb 24.

Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

A wide range of nitric oxide (NO)-releasing materials has emerged as potential therapeutics that exploit NO's vast biological roles. Macromolecular NO-releasing scaffolds are particularly promising due to their ability to store and deliver larger NO payloads in a more controlled and effective manner compared to low molecular weight NO donors. While a variety of scaffolds (e.g., particles, dendrimers, and polymers/films) have been cleverly designed, the ultimate clinical utility of most NO-releasing macromolecules remains unrealized. Although not wholly predictive of clinical success, in vitro and in vivo investigations have enabled a preliminary evaluation of the therapeutic potential of such materials. In this tutorial review, we review the application of macromolecular NO therapies for cardiovascular disease, cancer, bacterial infections, and wound healing.
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http://dx.doi.org/10.1039/c2cs15273hDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3341526PMC
May 2012

Influence of scaffold size on bactericidal activity of nitric oxide-releasing silica nanoparticles.

ACS Nano 2011 Sep 29;5(9):7235-44. Epub 2011 Aug 29.

Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.

A reverse microemulsion synthesis was used to prepare amine-functionalized silica nanoparticles of three distinct sizes (i.e., 50, 100, and 200 nm) with similar amine content. The resulting hybrid nanoparticles, consisting of N-(6-aminohexyl)aminopropyltrimethoxysilane and tetraethoxysilane, were highly monodisperse in size. N-Diazeniumdiolate nitric oxide (NO) donors were subsequently formed on secondary amines while controlling reaction conditions to keep the total amount of NO released constant for each particle size. The bactericidal efficacy of the NO-releasing nanoparticles against Pseudomonas aeruginosa increased with decreasing particle size. Additionally, smaller diameter nanoparticles were found to associate with the bacteria at a faster rate and to a greater extent than larger particles. Neither control (non-NO-releasing) nor NO-releasing particles exhibited toxicity toward L929 mouse fibroblasts at concentrations above their respective minimum bactericidal concentrations. This study represents the first investigation of the bactericidal efficacy of NO-releasing silica nanoparticles as a function of particle size.
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http://dx.doi.org/10.1021/nn202054fDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3225065PMC
September 2011

Fabrication of nitric oxide-releasing polyurethane glucose sensor membranes.

Biosens Bioelectron 2011 Oct 17;28(1):17-24. Epub 2011 Jun 17.

Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

Despite clear evidence that polymeric nitric oxide (NO) release coatings reduce the foreign body response (FBR) and may thus improve the analytical performance of in vivo continuous glucose monitoring devices when used as sensor membranes, the compatibility of the NO release chemistry with that required for enzymatic glucose sensing remains unclear. Herein, we describe the fabrication and characterization of NO-releasing polyurethane sensor membranes using NO donor-modified silica vehicles embedded within the polymer. In addition to demonstrating tunable NO release as a function of the NO donor silica scaffold and polymer compositions and concentrations, we describe the impact of the NO release vehicle and its release kinetics on glucose sensor performance.
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http://dx.doi.org/10.1016/j.bios.2011.06.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3186917PMC
October 2011

Nitric oxide-releasing silica nanoparticle inhibition of ovarian cancer cell growth.

Mol Pharm 2010 Jun;7(3):775-85

Department of Pharmacology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.

Although the potent antitumor activity of nitric oxide (NO) supports its promise as an antineoplastic agent, effective and selective delivery and action on tumor and not normal cells remains a limiting factor. Nanoparticle-based delivery of NO has been considered as one approach to overcome these limitations. Therefore, we determined the utility of NO delivery using silica nanoparticles and evaluated their antitumor efficacy against human ovarian tumor and nontumor cells. The NO-releasing nanoparticles exhibited enhanced growth inhibition of ovarian tumor cells when compared to both control nanoparticles and a previously reported small molecule NO donor, PYRRO/NO. In addition, the NO-releasing nanoparticles showed greater inhibition of the anchorage-independent growth of tumor-derived and Ras-transformed ovarian cells. Confocal microscopy analysis revealed that fluorescently labeled NO-releasing nanoparticles entered the cytosol of the cell and localized to late endosomes and lysosomes. Furthermore, we observed a nanoparticle size dependency on efficacy against normal versus transformed ovarian cells. Our study provides the first application of nanoparticle-derived NO as an antitumor therapy and merits future studies examining nanoparticle formulation for in vivo applications.
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http://dx.doi.org/10.1021/mp9002865DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3569608PMC
June 2010