Correction to 'Magnetic targeting of microbubbles against physiologically relevant flow conditions'.
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ABSTRACT:
SUBMITTER: Owen J
PROVIDER: S-EPMC4686253 | biostudies-literature | 2016 Feb
REPOSITORIES: biostudies-literature
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Project description:Ring opening metathesis polymerization (ROMP) is widely considered an excellent living polymerization technique that proceeds rapidly under ambient conditions and is highly functional group tolerant when performed in organic solvents. However, achieving the same level of success in aqueous media has proved to be challenging, often requiring an organic co-solvent or a very low pH to obtain fast initiation and high monomer conversion. The ability to efficiently conduct ROMP under neutral pH aqueous conditions would mark an important step towards utilizing aqueous ROMP with acid-sensitive functional groups or within a biological setting. Herein we describe our efforts to optimize ROMP in an aqueous environment under neutral pH conditions. Specifically, we found that the presence of excess chloride in solution as well as relatively small changes in pH near physiological conditions have a profound effect on molecular weight control, polymerization rate and overall monomer conversion. Additionally, we have applied our optimized conditions to polymerize a broad scope of water-soluble monomers and used this methodology to produce nanostructures via ring opening metathesis polymerization induced self-assembly (ROMPISA) under neutral pH aqueous conditions.
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Project description:Trehalose, a natural disaccharide, is primarily known for its ability to protect proteins from inactivation and denaturation caused by a variety of stress conditions. Furthermore, over the past few years, it has emerged as a promising therapeutic candidate for treatment of neurodegenerative diseases. Herein, we examine the attachment of trehalose to polymers for release under selected physiologically relevant conditions. The proposed strategies are evaluated specifically using hydrogels undergoing simultaneous degradation during trehalose release. These materials are fabricated via copolymerization of the appropriate acrylamide-type monomers with polymerizable trehalose esters or benzylidene acetals. This provides trehalose release in a slightly alkaline (i.e., pH 7.4) or mildly acidic (i.e., pH 5.0) environment, respectively. Using this method materials containing up to 51.7 wt% of trehalose are obtained. The presented results provide a solid basis for future studies on polymeric materials intended for trehalose release in biological systems.
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Project description:Peptide nucleic acids containing thymidine and 2-aminopyridine (M) nucleobases form stable and sequence-selective triple helices with double-stranded RNA at physiologically relevant conditions. The M-modified PNA showed unique RNA selectivity by having two orders of magnitude higher affinity for the double-stranded RNAs than for the same DNA sequences.
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Project description:Pseudomonas aeruginosa causes severe multi-drug resistant infections that often lead to bacteremia and sepsis. Physiologically relevant conditions can increase the susceptibility of pathogens to antibiotics, such as azithromycin (AZM). When compared to minimal inhibitory concentrations (MIC) in lab media, AZM had a 16-fold lower MIC in tissue culture medium with 5% MHB, and a 64-fold lower MIC in this tissue culture medium with 20% human serum. AZM also demonstrated increased synergy in combination with synthetic host defence peptides DJK-5 and IDR-1018 under host-like conditions and in a murine abscess model. To mechanistically study the altered effects of AZM under physiologically relevant conditions, global transcriptional analysis was performed on P. aeruginosa with and without effective concentrations of AZM. This revealed that the arn operon, mediating arabinosaminylation of lipopolysaccharides, and related regulatory systems, were downregulated in host-like media when compared to MHB. Inactivation of genes within the arn operon led to increased susceptibility of P. aeruginosa to AZM and great increases in synergy between AZM and other antimicrobial agents, indicating that dysregulation of the arn operon might explain increased AZM uptake and synergy in host-like media. Furthermore, genes involved in central and energy metabolism, and ribosome biogenesis were dysregulated more in physiologically relevant conditions treated with AZM, likely due to general changes in cell physiology as a result of the increased effectiveness of AZM in these conditions. These data suggest that, in addition to the arn operon, there are multiple factors in host-like environments that are responsible for observed changes in susceptibility.
2020-12-21 | GSE151259 | GEO
Project description:Dissolution rates of nanomaterials can be decisive for acute in vivo toxicity (via the released ions) and for biopersistence (of the remaining particles). Continuous flow systems (CFSs) can screen for both aspects, but operational parameters need to be adjusted to the specific physiological compartment, including local metal ion saturation. CFSs have two adjustable parameters: the volume flow-rate and the initial particle loading. Here we explore the pulmonary lysosomal dissolution of nanomaterials containing the metals Al, Ba, Zn, Cu over a wide range of volume flow-rates in a single experiment. We identify the ratio of particle surface area (SA) per volume flow-rate (SA/V) as critical parameter that superimposes all dissolution rates of the same material. Three complementary benchmark materials-ZnO (quick dissolution), TiO2 (very slow dissolution), and BaSO4 (partial dissolution)-consistently identify the SA/V range of 0.01 to 0.03 h/?m as predictive for lysosomal pulmonary biodissolution. We then apply the identified method to compare against non-nanoforms of the same substances and test aluminosilicates. For BaSO4 and TiO2, we find high similarity of the dissolution rates of their respective nanoform and non-nanoform, governed by the local ion solubility limit at relevant SA/V ranges. For aluminosilicates, we find high similarity of the dissolution rates of two Kaolin nanoforms but significant dissimilarity against Bentonite despite the similar composition.
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Project description:Carbon disulfide is an environmental toxin, but there are suggestions in the literature that it may also have regulatory and/or therapeutic roles in mammalian physiology. Thiols or thiolates would be likely biological targets for an electrophile, such as CS2, and in this context, the present study examines the dynamics of CS2 reactions with various thiols (RSH) in physiologically relevant near-neutral aqueous media to form the respective trithiocarbonate anions (TTC-, also known as "thioxanthate anions"). The rates of TTC- formation are markedly pH-dependent, indicating that the reactive form of RSH is the conjugate base RS-. The rates of the reverse reaction, that is, decay of TTC- anions to release CS2, is pH-independent, with rates roughly antiparallel to the basicities of the RS- conjugate base. These observations indicate that the rate-limiting step of decay is simple CS2 dissociation from RS-, and according to microscopic reversibility, the transition state of TTC- formation would be simple addition of the RS- nucleophile to the CS2 electrophile. At pH 7.4 and 37 °C, cysteine and glutathione react with CS2 at a similar rate but the trithiocarbonate product undergoes a slow cyclization to give 2-thiothiazolidine-4-carboxylic acid. The potential biological relevance of these observations is briefly discussed.
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Project description:Conjugation of short peptide nucleic acids (PNA) with tetralysine peptides strongly enhanced triple helical binding to RNA at physiologically relevant conditions. The PNA hexamers and heptamers carrying cationic nucleobase and tetralysine modifications displayed high binding affinity for complementary double-stranded RNA without compromising sequence selectivity. The PNA-peptide conjugates had unique preference for binding double-stranded RNA, while having little, if any, affinity for double-stranded DNA. The cationic PNAs were efficiently taken up by HEK293 cells, whereas little uptake was observed for unmodified PNA.
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Project description:Image-guided and target-selective modulation of drug delivery by external physical triggers at the site of pathology has the potential to enable tailored control of drug targeting. Magnetic microbubbles that are responsive to magnetic and acoustic modulation and visible to ultrasonography have been proposed as a means to realize this drug targeting strategy. To comply with this strategy in vivo, magnetic microbubbles must circulate systemically and evade deposition in pulmonary capillaries, while also preserving magnetic and acoustic activities in circulation over time. Unfortunately, challenges in fabricating magnetic microbubbles with such characteristics have limited progress in this field. In this report, we develop magnetic microbubbles (MagMB) that display strong magnetic and acoustic activities, while also preserving the ability to circulate systemically and evade pulmonary entrapment. METHODS:We systematically evaluated the characteristics of MagMB including their pharmacokinetics, biodistribution, visibility to ultrasonography and amenability to magneto-acoustic modulation in tumor-bearing mice. We further assessed the applicability of MagMB for ultrasonography-guided control of drug targeting. RESULTS:Following intravenous injection, MagMB exhibited a 17- to 90-fold lower pulmonary entrapment compared to previously reported magnetic microbubbles and mimicked circulation persistence of the clinically utilized Definity microbubbles (>10 min). In addition, MagMB could be accumulated in tumor vasculature by magnetic targeting, monitored by ultrasonography and collapsed by focused ultrasound on demand to activate drug deposition at the target. Furthermore, drug delivery to target tumors could be enhanced by adjusting the magneto-acoustic modulation based on ultrasonographic monitoring of MagMB in real-time. CONCLUSIONS:Circulating MagMB in conjunction with ultrasonography-guided magneto-acoustic modulation may provide a strategy for tailored minimally-invasive control over drug delivery to target tissues.
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Project description:Here, we used a saturated transposon insertion mutant pool of P. aeruginosa strain PAO1 and transposon insertion sequencing (Tn-Seq), to identify genes conditionally important for survival under conditions mimicking the environment of a nosocomial infection. Conditions tested included tissue culture medium with and without human serum, a murine abscess model, and a human skin organoid model.
2022-11-04 | GSE214167 | GEO
Project description:The development of methods to monitor manufactured nanomaterials in the environment is one of the crucial areas for the assessment of their risk. More specifically, particle size analysis is a key element, because many properties of nanomaterial are size dependent. The sizing of nanomaterials in real environments is challenging due to their heterogeneity and reactivity with other environmental components. In this study, the fractionation and characterization of a mixture of polyvinylpyrrolidone-coated silver nanoparticles (PVP-AgNPs) of three different sizes were investigated using asymmetrical flow field-flow fractionation (AF4) coupled with UV-Vis spectrophotometry. In particular, the effects of electrolyte composition and natural organic matter (NOM) on the particle size and stability were evaluated. The fractogram peaks (i.e., stability) of three different AgNPs decreased in the presence of both 10 mM NaCl and 10 mM CaCl2, while increased with increasing concentration of humic acid (HA). In addition, the hydrodynamic diameters of AgNPs in both electrolytes slightly increased with an increase of HA concentration, suggesting the adsorption (coating) of HA onto the particle surface. It is also interesting to note that an increase in the particle size depended on the types of electrolyte, which could be explained by the conformational characteristics of the adsorbed HA layers. Consistent these results, AgNPs suspended in lake water containing relatively high concentration of organic carbon (TOC) showed higher particle stability and larger particle size (i.e., by approximately 4 nm) than those in river water. In conclusion, the application of AF4 coupled with highly sensitive detectors could be a powerful method to characterize nanoparticles in natural waters.
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