102 research outputs found
Synthesis and Characterization of Cleavable Core-Cross-Linked Micelles Based on Amphiphilic Block Copolypeptoids as Smart Drug Carriers
Amphiphilic block copolypeptoids
consisting of a hydrophilic polyÂ(<i>N</i>-ethyl glycine)
segment and a hydrophobic polyÂ[(<i>N</i>-propargyl glycine)-<i>r</i>-(<i>N</i>-decyl glycine)] random copolymer segment
[PNEG-<i>b</i>-PÂ(NPgG-<i>r</i>-NDG), EPgD] have
been synthesized by sequential
primary amine-initiated ring-opening polymerization (ROP) of the corresponding <i>N</i>-alkyl <i>N</i>-carboxyanhydride monomers. The
block copolypeptoids form micelles in water and the micellar core
can be cross-linked with a disulfide-containing diazide cross-linker
by copper-mediated alkyne–azide cycloaddition (CuAAC) in aqueous
solution. Transmission electron microscopy (TEM) and dynamic light
scattering (DLS) analysis revealed the formation of spherical micelles
with uniform size for both the core-cross-linked micelles (CCLMs)
and non-cross-linked micelles (NCLMs) precursors for selective block
copolypeptoid polymers. The CCLMs exhibited increased dimensional
stability relative to the NCLMs in DMF, a nonselective solvent for
the core and corona segments. Micellar dissociation of CCLMs can be
induced upon addition of a reducing agent (e.g., dithiothreitol) in
dilute aqueous solutions, as verified by a combination of fluorescence
spectroscopy, size exclusion chromatography (SEC), and <sup>1</sup>H NMR spectroscopic measurement. Doxorubicin (DOX), an anticancer
drug, can be loaded into the hydrophobic core of CCLMs with a maximal
23% drug loading capacity (DLC) and 37% drug loading efficiency (DLE). <i>In vitro</i> DOX release from the CCLMs can be triggered by
DTT (10 mM), in contrast to significantly reduced DOX release in the
absence of DTT, attesting to the reductively responsive characteristic
of the CCLMs. While the CCLMs exhibited minimal cytotoxicity toward
HepG2 cancer cells, DOX-loaded CCLMs inhibited the proliferation of
the HepG2 cancer cells in a concentration and time dependent manner,
suggesting the controlled release of DOX from the DOX-loaded CCLMS
in the cellular environment
Naturally Occurring Incompatibilities between Different <em>Culex pipiens pallens</em> Populations as the Basis of Potential Mosquito Control Measures
<div><h3>Background</h3><p>Vector-borne diseases remain a threat to public health, especially in tropical countries. The incompatible insect technique has been explored as a potential control strategy for several important insect vectors. However, this strategy has not been tested in <em>Culex pipiens pallens</em>, the most prevalent mosquito species in China. Previous works used introgression to generate new strains that matched the genetic backgrounds of target populations while harboring a new <em>Wolbachia</em> endosymbiont, resulting in mating competitiveness and cytoplasmic incompatibility. The generation of these incompatible insects is often time-consuming, and the long-term stability of the newly created insect-<em>Wolbachia</em> symbiosis is uncertain. Considering the wide distribution of <em>Cx. pipiens pallens</em> and hence possible isolation of different populations, we sought to test for incompatibilities between natural populations and the possibility of exploiting these incompatibilities as a control strategy.</p> <h3>Methodology/Principal Findings</h3><p>Three field populations were collected from three geographic locations in eastern China. Reciprocal cross results showed that bi-directional patterns of incompatibility existed between some populations. Mating competition experiments indicated that incompatible males could compete with cognate males in mating with females, leading to reduced overall fecundity. F1 offspring from incompatible crosses maintained their maternal crossing types. All three populations tested positive for <em>Wolbachia</em>. Removal of <em>Wolbachia</em> by tetracycline rendered matings between these populations fully compatible.</p> <h3>Conclusions/Significance</h3><p>Our findings indicate that naturally occurring patterns of cytoplasmic incompatibility between <em>Cx. pipiens pallens</em> populations can be the basis of a control strategy for this important vector species. The observed incompatibilities are caused by <em>Wolbachia</em>. More tests including field trials are warranted to evaluate the feasibility of this strategy as a supplement to other control measures.</p> </div
Dynamic Covalent Polymer Networks Based on Degenerative Imine Bond Exchange: Tuning the Malleability and Self-Healing Properties by Solvent
Covalent
polymeric networks composed of imine cross-linkages have
been prepared by condensation polymerization of polyÂ(ethylene glycol)
bisÂ(3-aminopropyl) with 1,3,5-triformylbenzene with an equal molar
ratio of amine and aldehyde functionalities in organic solvents with
varying polarity and in neat condition. The polymer networks exhibit
malleability and self-healing characteristics. Rheological measurements
revealed that longer reaction time is required to reach the gel point
(i.e., crossover of <i>G</i>′ and <i>G</i>″) in polar solvents than in nonpolar solvents. The malleability
of the solvent-swelled polymer network is also strongly dependent
on the solvent polarity. Polymer gels in polar solvents are more malleable
than those in nonpolar solvents, as supported by the dynamic mechanical
analysis. These results are consistent with faster dynamic imine bond
exchange in the polar solvents relative to the nonpolar solvents,
thus requiring higher functionality conversion to form an elastic
network in the polar solvent relative to the nonpolar solvent. The
imine–imine bond exchange kinetic was also studied by <sup>1</sup>H NMR spectroscopy on model compounds in the presence of varying
amount of primary amine and water. The exchange reaction was significantly
accelerated by the presence of primary amine than water, suggesting
that the imine bond exchange is mainly promoted by the residual primary
amino functionalities in the polymeric network. This study revealed
the molecular and kinetic basis for the macroscopic and dynamical
properties of the polymer networks composed of imine cross-linkages.
The polymer networks are potentially useful as adhesives
Elimination of <i>Wolbachia</i> rendered TK and WX populations fully compatible.
<p>WX females were crossed with an equal number of tetracycline-treated TK males (TK<sub>tet</sub>♂), untreated TK males (TK♂) or WX males (WX♂). TK females were crossed with an equal number of tetracycline-treated WX males (WX<sub>tet</sub>♂), untreated WX males (WX♂) or TK males (TK♂). Hatching rates were calculated for these crosses. Error bars represent standard errors; ns, non-significant <i>P</i>-value; *** <i>P</i><0.0001 by <i>t</i>-test.</p
Reproductive compatibilities between three <i>Cx. pipiens pallens</i> field populations.
<p>Three <i>Cx. pipiens pallens</i> field populations NJ, WX and TK were used in reciprocal crosses to test their reproductive compatibilities. For each cross, an equal number of virgin females and males were kept in a cage for 48 hours before blood feeding. After oviposition, egg rafts were collected and allowed to hatch. The average hatching rates of these crosses were compared. (A) Mating combinations of NJ and WX populations, (B) Mating combinations of TK and WX populations, (C) Mating combinations of NJ and TK populations. Error bars represent standard errors; ns, non-significant <i>P</i>-value; *** <i>P</i><0.0001 by <i>t</i>-test.</p
Reproductive compatibilities of F1 offspring from incompatible crosses.
<p>F1 offspring from TK and WX crosses were mixed with TK, WX or the F1. The hatching rates were compared. (A) F1 from TK♀×WX♂ cross; (B) F1 from WX♀×TK♂ cross. Error bars represent standard errors; ns, non-significant <i>P</i>-value; *** <i>P</i><0.0001 by <i>t</i>-test.</p
Genes used for <i>Wolbachia</i> typing and their PCR amplification primers.
<p>Genes used for <i>Wolbachia</i> typing and their PCR amplification primers.</p
Collecting sites of <i>Cx. pipiens pallens</i> field populations.
<p>(A) The mosquito populations were collected from eastern China; (B) Three collecting sites Tangkou, Nanjing and Wuxi are shown in detail. The mosquito populations collected are designated TK, NJ and WX, respectively.</p
Effect of subsequent encounter with cognate males on the fecundity of the females retrieved from incompatible crosses.
<p>Females were retrieved from the two incompatible crosses as shown in <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0002030#pntd-0002030-g002" target="_blank">Figure 2B</a>. TK or WX females were equally divided into two subgroups, with one mixed with cognate males and the other kept alone (no male). After a second blood feeding and oviposition, egg rafts were collected and allowed to hatch. The average hatching rates of these subgroups were compared. Error bars represent standard errors; ns, non-significant <i>P</i>-value.</p
Correlation between group average hatching rate and the percentage of incompatible males.
<p>The average hatching rate of a group was plotted against the percentage of incompatible males which was calculated by dividing the number of incompatible males by the total number of males (incompatible and cognate). (A) TK females with TK and WX males; (B) WX females with WX and TK males.</p
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