The modulation of conjugated polyelectrolyte fluorescence response by nonionic surfactants is dependent on the structures of the surfactant and polymer, polymer average molecular weight, and ...polyelectrolyte–surfactant interactions. In this paper, we study the effect of nonionic n-alkyl polyoxyethylene surfactants (C i E j ) with different alkyl chain lengths (C i E5 with i = 6, 8, 10, and 12) and number of oxyethylene groups (C12E j with j = 5, 7, and 9) on the photophysics and ionic conductivity of poly{9,9-bis(6′-N,N,N-trimethylammonium)-hexyl-2,7-fluorene-alt-1,4-phenylene}bromide (HTMA-PFP) in dimethyl sulfoxide–water 4% (v/v). Molecular dynamics simulations show that HTMA-PFP chains tend to approach as the simulation evolves. However, the minimum distance between the polymer centers of mass increases upon addition of the surfactant and grows with both the surfactant alkyl chain length and the number of oxyethylene groups, although there are no specific polymer–surfactant interactions. A significant increase in the polymer emission intensity has been observed at surfactant concentrations around their critical micelle concentrations (cmcs), which is attributed to polymer aggregate disruption. However, an increase in the solution conductivity for concentrations above the C12E5 cmc has only been observed for the HTMA-PFP/C12E5 system. The enhancement of fluorescence emission intensity and conductivity upon surfactant addition increases with polymer average molecular weights and seems to be controlled by the polymer–surfactant proximity, which is maximum for C10E5 and C12E5.
Highlights • Imatinib and low-dose chemotherapy was effective in older adults and elderly patients with Ph-positive ALL. • Rituximab and specific chemotherapy were feasible and effective in mature ...B-cell ALL in older adults and elderly patients. • The outcome of Ph-ALL in elderly is dismal compared to Ph+ and mature B-cell ALL.
Biofilm formation by the pathobiont Haemophilus influenzae is associated with human nasopharynx colonization, otitis media in children, and chronic respiratory infections in adults suffering from ...chronic respiratory diseases such as chronic obstructive pulmonary disease (COPD). β-lactam and quinolone antibiotics are commonly used to treat these infections. However, considering the resistance of biofilm-resident bacteria to antibiotic-mediated killing, the use of antibiotics may be insufficient and require being replaced or complemented with novel strategies. Moreover, unlike the standard minimal inhibitory concentration assay used to assess antibacterial activity against planktonic cells, standardization of methods to evaluate anti-biofilm drug activity is limited. In this work, we detail a panel of protocols for systematic analysis of drug antimicrobial effect on bacterial biofilms, customized to evaluate drug effects against H. influenzae biofilms. Testing of two cinnamaldehyde analogs, (E)-trans-2-nonenal and (E)-3-decen-2-one, demonstrated their effectiveness in both H. influenzae inhibition of biofilm formation and eradication or preformed biofilms. Assay complementarity allowed quantifying the dynamics and extent of the inhibitory effects, also observed for ampicillin resistant clinical strains forming biofilms refractory to this antibiotic. Moreover, cinnamaldehyde analog encapsulation into poly(lactic-co-glycolic acid) (PLGA) polymeric nanoparticles allowed drug vehiculization while maintaining efficacy. Overall, we demonstrate the usefulness of cinnamaldehyde analogs against H. influenzae biofilms, present a test panel that can be easily adapted to a wide range of pathogens and drugs, and highlight the benefits of drug nanoencapsulation towards safe controlled release.
The competitive interaction has been studied between double-stranded DNA (dsDNA), the cationic conjugated polyelectrolyte (CPE) poly9,9-bis(6-N,N,N-trimethylamonium)hexyl)-fluorene-phenylene) bromide ...(HTMA-PFP) and anionic or neutral surfactants (sodium dodecyl sulfonate, SDSu, and n-dodecyl pentaoxyethylene glycol ether, C12E5) in 4% (v/v) dimethyl sulfoxide (DMSO)−water using UV/visible absorption and fluorescence spectroscopy. Dramatic changes are observed in the spectroscopic behavior of the system depending on the order of addition of the reagents, the surfactant charge, and concentration range. If the neutral C12E5 is added to the HTMA-PFP/dsDNA complex, no significant spectroscopic changes are observed. However, if SDSu is added to the same complex, a dramatic increase of the absorbance and emission intensity is observed for surfactant concentrations above the critical micelle concentration (cmc). In contrast, if dsDNA is added to HTMA-PFP/surfactant systems (with surfactant concentrations above their cmc) no significant changes are observed with SDSu, while a dramatic quenching of polymer emission is observed with C12E5, which can be explained quantitatively in terms of HTMA-PFP/surfactant/DNA complexation and the subsequent polymer aggregation upon charge neutralization. The results are compared with those for the binary systems (HTMA-PFP/DNA and HTMA-PFP/surfactants) and indicate the importance of electrostatic interactions between HTMA-PFP and oppositely charged species in the aggregation processes.
The well-structured β-phase emission of the neutral poly(9,9-dioctylfluorene) (PFO) is observed in 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) bilayers, either as polydisperse aqueous ...liposomes or as the lamellar phase in thin films, and has been characterized by absorption, fluorescence (steady-state and time-resolved), and fluorescence anisotropy spectroscopy. Inclusion of PFO in DMPC liposomes provides a way of obtaining the ordered structure of this neutral polymer in aqueous suspensions. Quantification of the increase of the PFO β-phase in DMPC liposomes with the increase in polymer concentration is followed by deconvolution of the absorption spectra. In solid films, the presence of the phospholipids enhances the β-phase formation. In addition, the effect of the PFO concentration on the phospholipid phase transitions has been studied by differential scanning calorimetry (in liposome) and polarized light thermal microscopy (in solid film), confirming PFO/DMPC interactions in both liposome and films. The liposome size and structure in the presence and absence of polymer were characterized by dynamic light scattering and transmission electron microscopy, which showed relatively modest changes in liposome shape but a decrease in size upon incorporation of PFO.
•In older adults intensive therapy yields better outcomes than semi-intensive therapy.•In these patients the frequency of HSCT in first CR is low.•As results of chemotherapy are poor, new therapy ...approaches are necessary.
The standardization of treatment of older adults with Philadelphia chromosome negative (Ph-) acute lymphoblastic leukemia (ALL) is challenging, especially in the age range of 55–65 years. This study aimed to compare intensive, pediatric-inspired therapy with non-intensive therapy in this population of patients.
The outcomes of 67 patients prospectively included in two consecutive pediatric-inspired intensive protocols (ALL-HR03 and ALL-HR11) from the Spanish PETHEMA Group were compared with those from 44 patients included in a contemporary semi-intensive protocol (ALL-OLD07).
Baseline patient and ALL characteristics were similar in both groups, except for a younger median age in the intensive group (medians: 58 vs. 62 years). Patients treated intensively had a higher complete remission rate (85% vs. 64%, p = 0.005), a lower cumulative incidence of relapse (39% 95%CI, 25% to 52% vs. 60% 95%CI, 38% to 77%, p = .003), a similar cumulative incidence of treatment-related mortality (28% 95% CI, 18%, 40% vs. 21% 95% CI, 10%, 34%) and superior event-free survival at 2 years (37% 95%CI, 25%–49%) vs. 21% 8%-34%, p = 0.002). On multivariable analysis the type of protocol was the only variable with independent significance for event-free survival (HR 95% CI: 2 1.3, 3, p = .002).
Compared with less intensive chemotherapy, pediatric-inspired intensive chemotherapy significantly improves the outcome of older adults with Ph-negative ALL in the age range of 55–65 years.
The interaction between three poly(9,9-bis(6-N,N,N-trimethylammonium)hexyl)fluorene phenylene) bromide (HTMA-PFP) samples of different molecular weights ( M n = 14.5, 30.1 and 61.3 kg/mol) and both ...dsDNA and ssDNA secondary structures has been studied using UV−visible absorption and fluorescence spectroscopies (including steady-state, time-resolved, and anisotropy measurements for the latter), viscosity, and electrical conductivity in 4% (v/v) DMSO−water mixtures. At low nucleic acid concentrations, formation of a 1:1 complex in terms of HTMA-PFP repeat units and DNA bases occurs. This interaction results in quenching of polymer emission. For higher molar ratios of DNA to HTMA-PFP, corresponding to charge neutralization, a second process is observed that is attributed to aggregate formation. From the changes in the absorption spectra, the polymer aggregation constant and the aggregate absorption spectra were calculated by applying an iterative method. Polymer aggregation dramatically quenches HTMA-PFP fluorescence in the region of the electroneutrality point. Under these conditions, the ratio of the emission intensity at 412 nm (maximum) to that at 434 nm (I 412/I 434) reaches a minimum, the electrical conductivity decreases, and the viscosity of the solution remains constant, showing that the DNA concentration can be determined through various HTMA-PFP physicochemical properties. With respect to the photophysical parameters (emission quantum yield, shape and shift of emission spectra), no significant differences were observed between dsDNA and ssDNA or with conjugated polymer or DNA molecular weight. The two short-lived components in the fluorescence decays are attributed to the presence of aggregates. Aggregates are also suggested to be responsible for the decrease in the fluorescence anisotropy through interchain exciton migration.
The diffusion behavior of the conjugated polyelectrolyte poly{9,9-bis(6′-N,N,N-trimethylammonium)hexylfluorene-phenylene} bromide (HTMA-PFP) with different molecular weights has been studied in ...dimethyl sulfoxide (DMSO) + water solutions. Samples of HTMA-PFP with various molecular weights were obtained by synthesis of poly9,9-bis(6′-bromohexyl)fluorene-phenylene via a Suzuki coupling reaction, characterized by size exclusion chromatography (SEC), and quaternized with trimethylamine. Multicomponent chemical interdiffusion coefficients (mutual diffusion coefficients) were determined for solutions of HTMA-PFP and DMSO in water using the Taylor dispersion method. The results suggest specific interactions between the DMSO and the polymer. In addition, these systems were studied by pulse-field gradient nuclear magnetic resonance spectroscopy (PFG-NMR), and the corresponding self-diffusion coefficients were obtained. These were modeled using the Kirkwood−Riseman model, and a good fit to the observed behavior was obtained using literature data for molecular dimensions.
We have studied the effect of head group and alkyl chain length on β‐phase formation in poly(9,9‐dioctylfluorene) (PFO) solubilized in phospholipid liposomes. Systems studied have three different ...alkyl chain lengths (1,2‐dimyristoyl‐sn‐glycero‐3‐phosphatidylcholine DMPC, 1,2‐didodecanoyl‐sn‐glycero‐3‐phosphatidylcholine DLPC, 1,2‐dipalmitoyl‐sn‐glycero‐3‐phosphatidylcholine DPPC) and head groups (1,2‐dimyristoyl‐sn‐glycero‐3‐phosphate monosodium salt DMPA, 1,2‐dimyristoyl‐sn‐glycero‐3‐phosphoethanolamine DMPE and 1,2‐dimyristoyl‐sn‐glycero‐3‐phospho‐l‐serine sodium salt DMPS). Changes in liposome size upon addition of PFO are followed by dynamic light scattering. All the phospholipids induce the formation of PFO β‐phase, which is followed by the emission intensity and deconvolution of the absorption spectra. Both the head group and alkyl chain length affect the yield of β‐phase. The photophysics of PFO incorporated in liposomes is characterized by stationary and time‐resolved fluorescence, whereas the polymer‐phospholipid interactions have been studied by the effect of the PFO concentration on the phospholipid phase transitions (differential scanning calorimetry DSC).
Poly(9,9‐dioctylfluorene) is solubilized in phospholipid liposomes of DLPC, DMPC, DPPC, DMPE, DMPA, and DMPS giving rise to the formation of the ordered polymer β‐phase which is characterized by a well‐resolved characteristic vibronic structure in the emission spectra, higher luminescence efficiency and improved charge transport properties resulting from increased electron delocalization. This phase is better promoted by phospholipids with longer alkyl chain lengths or non‐bulky and more hydrophobic head groups. The polymer agglomeration is considered the main mechanism for β‐phase formation in these systems. A second driving force seems to be the interdigitation between the polymer and phospholipid alkyl chains.
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