Control of Dynamics in Polyelectrolyte Complexes by Temperature and Salt

The linear viscoelastic responses for a series of polyelectrolyte complexes, PECs, made from pairs of poly­[3-(methacryloyl­amino)­propyl­trimethyl­ammonium chloride], a polycation, and poly­(sodium methacrylate), a polyanion, having various molecular weights were measured. Time–temperature superposition (TTS) for broad and narrow molecular weight distributions revealed entangled behavior at low salt concentration for the longer polyelectrolytes studied. All characteristic lifetimes were slowed by “sticky” dynamics of positive, Pol+ and negative, Pol–, pairing. Time–temperature–salt doping superposition (TTSS) was achieved by considering the dual effects of increasing salt concentration on PECs: the partner lifetimes of Pol+ and Pol– were inversely proportional to [NaCl], as was the population of Pol+Pol– pairs. Relaxation times for polymer partnering, entanglement, and reptation were measured directly on some systems. Whereas the intrinsic (in the absence of salt ions) lifetime for Pol+Pol– pairs was determined to be on the order of 1 × 10–4 s, salt doping provided a faster, extrinsic, channel for relaxation at the monomer scale. The time−salt shift factor was decomposed into contributions from Pol+Pol– partner lifetimes, the number density of Pol+Pol– pairs, and the volume fraction of polymer

Copper-Doped Platinum/Metal-Organic Framework Nanostructures for Imaging-Guided Photothermal and H₂O₂ Self-Supplying Photodynamic/Photothermal/Chemodynamic Therapy

Simultaneous photodynamic/photothermal therapy (PDT/PTT) is a combination cancer treatment that combines the principles of both PDT and PTT to achieve an effective and comprehensive attack on cancer cells. However, both approaches require an external light source to generate reactive oxygen species (ROS) and thermal heat, which could potentially hinder the therapeutic efficacy due to the low tissue penetration of light in vivo. Chemodynamic therapy (CDT) is a type of therapy that uses the ROS generated by the chemical reaction between a prodrug and a catalyst to kill cancer cells. We developed a combination therapy of three modalities (PTT/PDT/CDT) using the metal-organic framework (MOF). The Cu2+-doped MOF PCN-224 nanostructures modified with platinum (Pt) cluster and folic acid (FA) provided excellent tumor targeting, photothermal conversion ability, and ROS generated by the Pt cluster and Cu2+ under 650 nm light irradiation. Moreover, this multimodel nanocomposite had an extremely low dark toxicity but excellent phototoxicity under the combination laser irradiation at 650 nm, both in vitro and in vivo. Therefore, our prepared folic acid-conjugated PCN-224/Pt/Cu2+ (FA-PPC) nanosphere could be applied as a very promising multimodal phototherapeutic agent for enhanced cancer therapy in future clinical applications

Ion Content of Polyelectrolyte Complex Coacervates and the Donnan Equilibrium

Oppositely charged polyelectrolytes in solution spontaneously associate into hydrated complexes or coacervates, PECs. The morphology, stability, and properties of PECs depend strongly on their ion content, which moderates the “sticky” reversible interactions between Pol+ and Pol– oppositely charged repeat units. Here, it is shown that the distribution of ions between a PEC and the aqueous solution in which it is immersed is accurately predicted by the Donnan equilibrium. For ideal, stoichiometric mixing of polyelectrolytes, corresponding to an enthalpy of complexation ΔHPEC → 0, the salt, MA, concentration inside the PEC, [MA]PEC, is equal to the solution salt concentration, [MA]s. Isothermal calorimetry measurements along a Hofmeister series show that if mixing is exothermic, [MA]PEC < [MA]s, while for endothermic association of Pol+ and Pol–, [MA]PEC > [MA]s. A set of simple self-consistent expressions illustrate PEC salt response without consideration of net Coulombic or electrostatic forces between charged species. ΔHPEC exactly predicts deviations from ideal Donnan equilibria, which are connected to the equilibria between associated or intrinsic pairs of Pol+Pol– and extrinsic Pol+A– and Pol–M+ pairs, where counterions compensate polyelectrolyte charges. The equilibrium constant Kpair for Pol+Pol– pair formation is shown to be proportional to the volume charge density of the hydrated, ion-free complex. Kpair may also be used to estimate the critical salt concentration at which polyelectrolytes completely dissociate

Additional file 1 of NIR-II-driven and glutathione depletion-enhanced hypoxia-irrelevant free radical nanogenerator for combined cancer therapy

Additional file 1: Figure S1. (a) Hydrodynamic diameter of APCZ within 14-day dialysis in PBS buffer (pH 7.4). (b) Zeta potentials of aqueous APCZ dispersion before and after 14 day’s dialysis in PBS buffer (pH 7.4). Data shown as mean ± SD, n = 3 per treatment. Figure S2. (a) UV–vis absorption spectra of AIPH at various concentrations. (b) Standard curve of AIPH determined from (a) at 364 nm. Figure S3. UV–vis absorption spectra of AIPH before and after loading (solutions were diluted 5-fold for measurements). Figure S4. Photothermal curves of aqueous PDA (48.16 µg mL−1) and PVP-CuS (22.78 µg mL−1) dispersions exposed to a 1064 nm laser (1.0 W cm−2, 10 min). Figure S5. UV–vis absorption spectra of DTNB at various concentrations (10 −50 µM). Figure S6. (a) UV–vis absorption spectra of DTNB (25 µM) with various concentrations of GSH (12.5, 25, 37.5, and 50 µM). (b) Standard curve determined from (a) at 412 nm. Figure S7. Detection of GSH (50 µM) depletion by various concentrations of AP dispersions (5, 10, 15, 20 and 25 µg mL−1) after 12 h of reaction. [DTNB] = 25 µM. Figure S8. The degradation of AP in GSH, acid (pH 5.0) and acidic GSH (pH 5.0) for 12 h. [GSH] = 1 mM, [AP] = 100 µg mL−1. Figure S9. Detection of GSH (50 µM) depletion by aqueous CuCl2 (50 µM) solution for 10, 30, 60, 120, 180, 240 and 360 min, respectively. [DTNB] = 25 µM. Figure S10. UV–vis absorption spectra of PVP-CuS (25 µg mL−1) after incubation with various concentrations of GSH (0, 1, 2, 4 and 10 mM) for 6 h. Figure S11. Digital photos of PVP-CuS/GSH mixtures (separated by centrifugation and re-dispersed in 400 µL of DI H2O) after 6 h of reaction. [PVP-CuS] = 25 µg mL−1, [GSH] = (1) 0 mM, (2) 1 mM, (3) 2 mM, (4) 4 mM and (5) 10 mM. Figure S12. Relative Cu ions release from PVP-CuS/GSH mixtures after incubation for 6 h. [PVP-CuS] = 25 µg mL−1, [GSH] = 1, 2, 4 and 10 mM. Figure S13. TEM images of (a) PVP-CuS and (b-f) PVP-CuS/GSH mixtures after 24 h of reaction. [PVP-CuS] = 25 µg mL−1, [GSH] = 10 mM. Figure S14. Cumulative AIPH release profile of APCZ in PBS buffer of pH 7.4, pH 7.4 + GSH (10 mM), pH 5.0 and pH 5.0 + GSH (10 mM) for 24 h. Data shown as mean ± SD, n = 3 per treatment. Figure S15. Cumulative Cu ions release profile of APCZ in PBS buffer of pH 7.4, pH 7.4 + GSH (10 mM), pH 7.4 + GSH (10 mM) + Laser, pH 5.0, pH 5.0 + GSH (10 mM) and pH 5.0 + GSH (10 mM) + Laser. The orange arrows represented laser (1064 nm, 1.0 W cm−2) treatment, each time point was radiated for 10 min. Data shown as mean ± SD, n = 3 per treatment. Figure S16. UV–vis−NIR absorption spectra of APCZ and APCZ/GSH mixture after incubation in aqueous ABTS solution (44 °C) for 6 h. [APCZ] = 400 µg mL−1, [GSH] = 0.5 mM, [ABTS] = 20 µg mL−1. Figure S17. IC50 of PCZ group in normoxic condition calculated from MTT results by GraphPad Prism 8 software. Figure S18. (a) The blood clearance kinetics of APCZ after intravenously administration. (b) Biodistribution analysis of APCZ in 4T1 tumor bearing mice after the tail vein injection for 24 and 48 h. Data shown as mean ± SD, n = 3 per treatment. Figure S19. Standard curves of (a) mouse TNF-α and (b) mouse IFN-γ. O.D. means optical density (absorbance at 450 nm). (c) TNF-α and (d) IFN-γ levels in sera isolated from different groups after 7-day treatments. Data shown as mean ± SD, n = 3 per treatment. Statistical significance was set at *p < 0.05, **p < 0.01, ***p < 0.001. Figure S20. H&E staining images of major organs after different treatments. Scale bars = 50 μm. Table S1. IC50 of different groups calculated from MTT results by GraphPad Prism 8 software

Data_Sheet_1_Antimicrobial susceptibility profiles and tentative epidemiological cutoff values of Legionella pneumophila from environmental water and soil sources in China.PDF

Legionnaires’ disease (LD), caused by Legionella, including the most prevalent Legionella pneumophila, has been treated primarily with antibiotics. Environmental water and soil are the reservoirs for L. pneumophila. Studying antimicrobial susceptibility using a large number of isolates from various environmental sources and regions could provide an unbiased result. In the present study, antimicrobial susceptibility of 1464 environmental L. pneumophila isolates that were derived from various environmental water and soil sources of 12 cities in China to rifampin (RIF), erythromycin (ERY), clarithromycin (CLA), azithromycin (AZI), ciprofloxacin (CIP), moxifloxacin (MOX), levofloxacin (LEV), and doxycycline (DOX) was investigated, and minimum inhibitory concentration (MIC) data were obtained. We show that regarding macrolides, ERY was least active (MIC90 = 0.5 mg/L), while CLA was most active (MIC90 = 0.063 mg/L). A total of three fluoroquinolones have similar MICs on L. pneumophila. Among these antimicrobials, RIF was the most active agent, while DOX was the most inactive one. We observed different susceptibility profiles between serogroup 1 (sg1) and sg2-15 or between water and soil isolates from different regions. The ECOFFs were ERY and AZI (0.5 mg/L), RIF (0.002 mg/L), CIP, CLA and MOX (0.125 mg/L), LEV (0.063 mg/), and DOX (32 mg/L). Overall, two fluoroquinolone-resistant environmental isolates (0.14%) were first documented based on the wild-type MIC distribution. Not all azithromycin-resistant isolates (44/46, 95.65%) harbored the lpeAB efflux pump. The MICs of the ERY and CLA on the lpeAB + isolates were not elevated. These results suggested that the lpeAB efflux pump might be only responsible for AZI resistance, and undiscovered AZI-specific resistant mechanisms exist in L. pneumophila. Based on the big MIC data obtained in the present study, the same defense strategies, particularly against both CLA and RIF, may exist in L. pneumophila. The results determined in our study will guide further research on antimicrobial resistance mechanisms of L. pneumophila and could be used as a reference for setting clinical breakpoints and discovering antimicrobial-resistant isolates in the clinic, contributing to the antibiotic choice in the treatment of LD.</p

Table_2_Antimicrobial susceptibility profiles and tentative epidemiological cutoff values of Legionella pneumophila from environmental water and soil sources in China.XLSX

Legionnaires’ disease (LD), caused by Legionella, including the most prevalent Legionella pneumophila, has been treated primarily with antibiotics. Environmental water and soil are the reservoirs for L. pneumophila. Studying antimicrobial susceptibility using a large number of isolates from various environmental sources and regions could provide an unbiased result. In the present study, antimicrobial susceptibility of 1464 environmental L. pneumophila isolates that were derived from various environmental water and soil sources of 12 cities in China to rifampin (RIF), erythromycin (ERY), clarithromycin (CLA), azithromycin (AZI), ciprofloxacin (CIP), moxifloxacin (MOX), levofloxacin (LEV), and doxycycline (DOX) was investigated, and minimum inhibitory concentration (MIC) data were obtained. We show that regarding macrolides, ERY was least active (MIC90 = 0.5 mg/L), while CLA was most active (MIC90 = 0.063 mg/L). A total of three fluoroquinolones have similar MICs on L. pneumophila. Among these antimicrobials, RIF was the most active agent, while DOX was the most inactive one. We observed different susceptibility profiles between serogroup 1 (sg1) and sg2-15 or between water and soil isolates from different regions. The ECOFFs were ERY and AZI (0.5 mg/L), RIF (0.002 mg/L), CIP, CLA and MOX (0.125 mg/L), LEV (0.063 mg/), and DOX (32 mg/L). Overall, two fluoroquinolone-resistant environmental isolates (0.14%) were first documented based on the wild-type MIC distribution. Not all azithromycin-resistant isolates (44/46, 95.65%) harbored the lpeAB efflux pump. The MICs of the ERY and CLA on the lpeAB + isolates were not elevated. These results suggested that the lpeAB efflux pump might be only responsible for AZI resistance, and undiscovered AZI-specific resistant mechanisms exist in L. pneumophila. Based on the big MIC data obtained in the present study, the same defense strategies, particularly against both CLA and RIF, may exist in L. pneumophila. The results determined in our study will guide further research on antimicrobial resistance mechanisms of L. pneumophila and could be used as a reference for setting clinical breakpoints and discovering antimicrobial-resistant isolates in the clinic, contributing to the antibiotic choice in the treatment of LD.</p

Influence of Nonstoichiometry on the Viscoelastic Properties of a Polyelectrolyte Complex

Depending on conditions such as the mixing ratio, speed and order of addition, and ionic strength, when solutions of oppositely charged polyelectrolytes are mixed, the stoichiometry of the formed polyelectrolyte complexes (PECs) can vary. In fact, for most conditions, some degree of nonstoichiometry is inevitable because the ratios of positive and negative charges do not “lock” themselves to 1:1, as was believed in some early work. PEC morphologies and mechanical properties depend on the molar ratio between the polycation and polyanion. In this work, poly­(diallyldimethylammonium) and poly­(styrene sulfonate) were used to make PECs with varying stoichiometries. PECs that were overcompensated with one polyelectrolyte were shown to have lower glass transition temperatures and moduli due to the plasticizing effect caused by increased water content. In addition, time–temperature superposition revealed a correlation between segmental relaxation times and stoichiometry. Nonstoichiometric PECs were shown to have elevated fractional free volumes and decreased polymer volume fractions, which are responsible for changes in their mechanical properties

Salt Resistance as a Measure of the Strength of Polyelectrolyte Complexation

When mixed, solutions of positive and negative polyelectrolytes may spontaneously phase-separate into blended, hydrated complexes or coacervates (PECs). Charge-pairing interactions between oppositely-charged polyelectrolytes within PECs are weakened with the addition of salt MA. With a sufficiently high concentration of MA, the PEC may dissociate back into the individual polyelectrolytes, reversing the liquid–liquid phase separation induced by charge pairing and other interactions. This critical salt concentration (CSC), or “salt resistance,” has been extensively used to compare the stability and strength of association in PECs. However, the CSC is not always observed, and it shows a strong dependence on the type of ions comprising MA. In addition, the CSC is more likely to be observed with PECs assembled from polycarboxylates, a type of weak polyelectrolyte. Here, it is shown that a lack of experimental CSC is correlated with the preferred role of ions M+ and A– in the PEC, counterion versus co-ion, or the specificity of a particular ion for a particular polyelectrolyte repeat unit, revealed by calorimetric measurements. The importance of the enthalpy of ionization of weak polyelectrolytes in providing an experimentally measurable CSC is quantitatively demonstrated

Data for: Dynamic Design and Vibration Testing of CFRP Drive-line System Used in Heavy-duty Machine Tool

The data provide the vibration testing results, data matrix of transfer matrix method and the FEA. The vibration testing results include the acceleration, frequency response and vibration displacement of both CFRP and metal driveline in each testing speed