53,355 research outputs found
Dexamethasone enhances insulin-like growth factor-I (IGF-I) stimulation of DNA synthesis in L6 myoblasts: studies on potential signalling mechanisms.
No full text
Autographa californica Multicapsid Nucleopolyhedrovirus efficiently infects Sf9 cells and transduces mammalian cells via direct fusion with the plasma membrane at low pH
No full textThe budded virus (BV) of the Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV) infects insect cells and transduces mammalian cells mainly through the endocytosis pathway. However, this study revealed that the treatment of the virus bound to Sf9 cells at low pH could efficiently rescue the infectivity of AcMNPV in the presence of endocytosis pathway inhibitors. A colocalization assay of the major capsid protein VP39 with the early endosome marker EEA1 showed that at low pH, AcMNPV entered Sf9 cells via an endosome-independent pathway. Using a fluorescent probe (R18), we showed that at low pH, the viral nucleocapsid entered Sf9 cells via direct fusion at the cell surface. By using the myosin-specific inhibitor 2,3-butanedione monoxime (BDM) and the microtubule inhibitor nocodazole, the low pH-triggered direct fusion was demonstrated to be dependent on myosin-like proteins and independent of microtubules. The reverse transcription-PCR of the IE1 gene as a marker for viral entry showed that the kinetics of AcMNPV in cells triggered by low pH was similar to that of the normal entry via endocytosis. The low pH-mediated infection assay and VP39 and EEA1 colocalization assay also demonstrated that AcMNPV could efficiently transduce mammalian cells via direct membrane fusion at the cell surface. More importantly, we found that a low-pH trigger could significantly improve the transduction efficiency of AcMNPV in mammalian cells, leading to the potential application of this method when using baculovirus as a vector for heterologous gene expression and for gene therap
Poly(2-(diethylamino)ethyl methacrylate)-based, pH-responsive, copolymeric mixed micelles for targeting anticancer drug control release
No full textQuan Chen,1 Siheng Li,2 Zixiong Feng,1 Meng Wang,3 Chengzhi Cai,2 Jufang Wang,3 Lijuan Zhang1 1School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, People’s Republic of China; 2Department of Chemistry, University of Houston, Houston, TX, USA; 3School of Bioscience & Bioengineering, South China University of Technology, Guangzhou, People’s Republic of China Abstract: We have demonstrated a novel drug delivery system to improve the selectivity of the current chemotherapy by pH-responsive, polymeric micelle carriers. The micelle carriers were prepared by the self-assembly of copolymers containing the polybasic poly(2-(diethylamino)ethyl methacrylate) (PDEAEMA) block. The mixed copolymers exhibited a comparatively low critical micelle concentration (CMC; 1.95–5.25 mg/L). The resultant mixed micelles were found to be <100 nm and were used to encapsulate the anticancer drug doxorubicin (DOX) with pretty good drug-loading content (24%) and entrapment efficiency (55%). Most importantly, the micelle carrier exhibited a pH-dependent conformational conversion and promoted the DOX release at the tumorous pH. Our in vitro studies demonstrated the comparable level of DOX-loaded mixed micelle delivery into tumor cells with the free DOX (80% of the tumor cells were killed after 48 h incubation). The DOX-loaded mixed micelles were effective to inhibit the proliferation of tumor cells after prolonged incubation. Overall, the pH-responsive mixed micelle system provided desirable potential in the controlled release of anticancer therapeutics. Keywords: PDEAEMA, copolymers, pH-responsive, mixed micelle, DOX, targeting deliver
Designing pH-Responsive Biodegradable Polymer Coatings for Controlled Drug Release via Vapor-Based Route
No full textWe present the design of a novel pH-responsive drug release system that is achieved by solventless encapsulation of drugs within a microporous membrane using a thin capping layer of biodegradable poly(methacrylic anhydride) (PMAH) coating. The coating was synthesized via a mild vapor polymerization process, namely, initiated chemical vapor deposition, which allowed perfect retention of the anhydride groups during deposition. The synthesized polyanhydride underwent degradation upon exposure to aqueous buffers, resulting in soluble poly(methacrylic acid). The degradation behavior of PMAH is highly pH-dependent, and the degradation rate under pH 10 is 15 times faster than that under pH 1. The release profile of a model drug rifampicin clearly exhibited two stages: the initial stage when the coatings were being degraded but the drugs were well stored and the second stage when drugs were gradually exposed to the medium and released. The drug release also showed strong pH responsiveness where the duration of the initial stage under pH 1 was more than 7 and 3 times longer than that under pH 10 and 7.4, respectively, and the release rates at pH 7.4 and 10 were significantly faster than that at pH 1. The pH-dependent degradation of the encapsulant thus enabled good preservation of drugs under low pH environment but high drug release efficiency under neutral and alkaline environment, suggesting potential applications in site-specific drug delivery systems
PH-responsive polymeric materials for encapsulation and triggered release
Full text linkThe strong research interest in encapsulation chemistry for functional chemical species (commonly referred to as active ingredients or actives) arises from the need to devise tailored strategies to protect precious actives from premature degradation or leakage. Furthermore, to maximize the performance of the encapsulated actives, a controllable method is needed to release the materials at the desired time, location, and rate. To address these challenges, scientists look to stimuli-responsive polymers as a solution because polymers can be designed with tailored properties thanks to advancement in polymer chemistry and engineering. This dissertation discloses a collaborative effort between the Zimmerman group and Dow Chemical to develop novel pH-responsive polymeric materials for encapsulation and triggered-release.
As a release trigger, pH is attractive because of the prevalence of environments with specific pH levels. In the first part of the dissertation, a diester diacid chloride monomer, PDDC, was utilized in the preparation of a novel pH-responsive polyamide microcapsule. PDDC was selected for its susceptibility to hydrolysis as well as simplicity in structure and synthesis. A mixture of polyamine monomers, which includes a triazine trisamine crosslinker and the commercially available DETA, reacted with PDDC to afford toluene-loaded (ca. 95% by weight), free-flowing microcapsules through interfacial polymerization. Through dye release experiments, the triazine-DETA-PDDC microcapsules exhibited a unique pH-dependent release behavior: similarly fast, first order like release profiles at pH 5 and pH 10 and a steady, linear release profile at pH 7.4. In a dry or hydrophobic environment, the microcapsules remained stable without UV-Vis detectable dye release or rapid loss of the volatile core solvent. In summary, the PDDC polyamide chemistry utilizes a single set of synthetically scalable monomers to prepare multi-pH responsive microcapsules that could see applications in different pH environments.
The second portion of the dissertation concerns a novel polyacetal that utilizes a new mechanism to facilitate degradation. A small molecule model compound containing the novel acetal moiety was synthesized and confirmed by NMR to show the expected degradation products under an acidic environment. Linear polymers bearing the novel acetal repeat unit were synthesized, with molecular weight up to 50 kDa as calibrated by PS standards. Crosslinked microcapsules bearing the novel acetal repeat unit were fabricated by interfacial polymerization. Encapsulation of a hydrophobic photoacid generator (PAG) in the core of the microcapsules demonstrated UV-triggered degradation.Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2019-12-01The student, Hsuan-Chin Wang, accepted the attached license on 2017-10-19 at 02:45.The student, Hsuan-Chin Wang, submitted this Dissertation for approval on 2017-10-19 at 02:49.This Dissertation was approved for publication on 2017-10-23 at 15:57.DSpace SAF Submission Ingestion Package generated from Vireo submission #11690 on 2019-08-22 at 16:17:30Made available in DSpace on 2019-08-23T20:44:16Z (GMT). No. of bitstreams: 3
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Reason: Author requested closed access (OA after 2yrs) in Vireo ETD systemEmbargo set by: Seth Robbins for item 112230
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Studies Towards a pH-Sensitive Anticancer Prodrug Model
No full textTumour-activated prodrug (TAP) is designed to aim at increasing the prodrug selectivity to kill cancer cells. One strategy to is to design a TAP containing an amine cytotoxin, present as an amide function, which could be released more rapidly in the low pH environment of tumour tissues when amide undergoes hydrolysis.
The prodrug model (1) was the subject of the current study. At lower pH its un-ionised carboxylic acid group provides neighbouring catalysis of hydrolysis of the adjacent amide. It was synthesised via ring-opening of the imide (2) which itself was directly synthesised from endo-bicyclo[2.2.2]octa-5-ene-2,3-dicarboxylic anhydride and p-methoxyaniline.
The pH-rate profile of (1) was established over the pH range of 3-10, covering rapid hydrolysis of un-ionised acid-amide at lower pH but slower imide formation above pH 8 from the ionised acid-amide. From the kinetic data were calculated the dissociation constant for (1) (pKa: 5.1 at 30 C) and limiting lower pH rate constant for hydrolysis of (1) in its fully neutral form (klim: 0.44 min-1 at 30 C). The data in the pH range of 8-10 provided klow (0.067 min-1) representing formation of (2) from fully ionised (1).
The following equilibrium reaction was also investigated at high pH, at which (1) was in its fully ionised amide carboxylate form, by kinetic studies on (2) in hydroxide solutions.
Imide + OH- Amide carboxylate
The second order rate constant for the forward reaction, kf, was 74 L mol-1 min-1 which with klow for the reverse reaction gave K as 1100 L mol-1
Red emitting and highly stable carbon dots with dual response to pH values and ferric ions
No full textThe authors describe strongly red-emitting carbon dots (CDs) which were obtained via microwave synthesis using phenylenediamine as the carbon source. The structural and optical properties of the resultant CDs are studied in some detail. The CDs possess (a) longwave emission (peaking at 620 nm under 470 nm excitation), (b) a quantum yield of similar to 15%, (c) a size of typically 3.8 nm; and (d) good photostability. The CDs have a pH-dependet response that covers the pH 5 to 10 range, and their fluorescence is quenched by ferric ions. The CDs can detect ferric ions in aqueous samples in the 0 to 30 mu M concentration range with a lower detection limit of 15 nM. The CDs were also used to image pH values and ferric ions in E. coli bacteria
In vitro antitumor activity of methotrexate via pH-sensitive chitosan nanoparticles
Full text linkNanoparticles with pH-sensitive behavior may enhance the success of chemotherapy in many cancers by efficient intracellular drug delivery. Here, we investigated the effect of a bioactive surfactant with pH-sensitive properties on the antitumor activity and intracellular behavior of methotrexate-loaded chitosan nanoparticles (MTX-CS-NPs). NPs were prepared using a modified ionotropic complexation process, in which was included the surfactant derived from Nα,Nε-dioctanoyl lysine with an inorganic lithium counterion. The pH-sensitive behavior of NPs allowed accelerated release of MTX in an acidic medium, as well as membrane-lytic pH-dependent activity, which facilitated the cytosolic delivery of endocytosed materials. Moreover, our results clearly proved that MTX-CSNPs were more active against the tumor HeLa and MCF-7 cell lines than the free drug. The feasibilty of using NPs to target acidic tumor extracellular pH was also shown, as cytotoxicity against cancer cells was greater in a mildly acidic environment. Finally, the combined physicochemical and pH-sensitive properties of NPs generally allowed the entrapped drug to induce greater cell cycle arrest and apoptotic effects. Therefore, our overall results suggest that pH-sensitive MTX-CS-NPs could be potentially useful as a carrier system for tumor and intracellular drug delivery in cancer therapy
Soil organic matter priming: The pH effects
No full textAbstract Priming of soil organic matter (SOM) decomposition by microorganisms is a key phenomenon of global carbon (C) cycling. Soil pH is a main factor defining priming effects (PEs) because it (i) controls microbial community composition and activities, including enzyme activities, (ii) defines SOM stabilization and destabilization mechanisms, and (iii) regulates intensities of many biogeochemical processes. In this critical review, we focus on prerequisites and mechanisms of PE depending on pH and assess the global change consequences for PE. The highest PEs were common in soils with pH between 5.5 and 7.5, whereas low molecular weight organic compounds triggered PE mainly in slightly acidic soils. Positive PEs up to 20 times of SOM decomposition before C input were common at pH around 6.5. Negative PEs were common at soil pH below 4.5 or above 7 reflecting a suboptimal environment for microorganisms and specific SOM stabilization mechanisms at low and high pH. Short‐term soil acidification (in rhizosphere, after fertilizer application) affects PE by: mineral‐SOM complexation, SOM oxidation by iron reduction, enzymatic depolymerization, and pH‐dependent changes in nutrient availability. Biological processes of microbial metabolism shift over the short‐term, whereas long‐term microbial community adaptations to slow acidification are common. The nitrogen fertilization induced soil acidification and land use intensification strongly decrease pH and thus boost the PE. Concluding, soil pH is one of the strongest but up to now disregarded factors of PE, defining SOM decomposition through short‐term metabolic adaptation of microbial groups and long‐term shift of microbial communities
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