Deuterated Curcuminoids: Synthesis,Structures, Computational/Docking and Comparative Cell Viability Assays against Colorectal Cancer

A series of deuterated curcuminoids (CUR) were synthesized, bearing two to six OCD₃ groups, in some cases in combination with methoxy groups, and in others together with fluorine or chlorine atoms. A model ring-deuterated hexamethoxy-CUR–BF₂ and its corresponding CUR compound were also synthesized from a 2,4,6-trimethoxybenzaldehyde-3,5-d₂ precursor. As with their protio analogues, the deuterated compounds were found to remain exclusively in the enolic form. The antiproliferative activities of these compounds were studied by in vitro bioassays against a panel of 60 cancer cell lines, and more specifically in human colorectal cancer (CRC) cells (HCT116, HT29, DLD-1, RKO, SW837, and Caco2) and in normal colon cells (CCD841CoN). The deuterated CUR–BF₂ adducts exhibited better overall growth inhibition by NCI-60 assay, while for other CUR–BF₂ adducts the non-deuterated analogues were more cytotoxic. Results of the more focused comparative cell viability assays followed the same trend, but with some variation depending on cell lines. The CUR–BF₂ adducts exhibited significantly higher cytotoxicity than CURs. Structural studies (X-ray and DFT) and computational molecular docking calculations comparing their inhibitory efficacy with those of known anticancer agents used in chemotherapy are also reported.     

Self-assembly behaviors of thermal- and pH- sensitive magnetic nanocarriers for stimuli-triggered release

In the present work, we prepare thermo- and pH-sensitive polymer-based nanoparticles incorporating with magnetic iron oxide as the remote-controlled, stimuli-response nanocarriers. Well-defined, dual functional tri-block copolymer poly[(acrylic acid)-block-(N-isopropylacrylamide)-block-(acrylic acid)], was synthesized via reversible addition-fragmentation chain-transfer (RAFT) polymerization with S,S′-bis(α,α′-dimethyl-α″-acetic acid)trithiocarbonate (CMP) as a chain transfer agent (CTA). With the aid of using 3-aminopropyltriethoxysilane, the surface-modified iron oxides, Fe₃O₄-NH₂, was then attached on the surface of self-assembled tri-block copolymer micelles via 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride/N-hydroxysuccinamide (EDC/NHS) crosslinking method in order to furnish not only the magnetic resources for remote control but also the structure maintenance for spherical morphology of our nanocarriers. The nanocarrier was characterized by transmission electron microscope (TEM), Fourier transform infrared spectroscopy (FT-IR), and ultraviolet–visible (UV/Vis) spectral analysis. Rhodamine 6G (R6G), as the modeling drugs, was encapsulated into the magnetic nanocarriers by a simple swelling method for fluorescence-labeling and controlled release monitoring. Biocompatibility of the nanocarriers was studied via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, which revealed that neither the pristine nanocarrier nor the R6G-loaded nanocarriers were cytotoxic to the normal fibroblast cells (L-929 cells). The in vitro stimuli-triggered release measurement showed that the intelligent nanocarriers were highly sensitive to the change of pH value and temperature rising by the high-frequency magnetic field (HFMF) treatment, which provided the significant potential to apply this technology to biomedical therapy by stimuli-responsive controlled release.     

Synthesis,Computational Docking Study,and Biological Evaluation of a Library of Heterocyclic Curcuminoids with Remarkable Antitumor Activity

In a continuing search for curcuminoid (CUR) compounds with antitumor activity, a novel series of heterocyclic CUR–BF₂ adducts and CUR compounds based on indole, benzothiophene, and benzofuran along with their aryl pyrazoles were synthesized. Computational docking studies were performed to compare binding efficiency to target proteins involved in specific cancers, namely HER2, proteasome, VEGFR, BRAF, and Bcl‐2, versus known inhibitor drugs. The majority presented very good binding affinities, similar to, and even more favorable than those of known inhibitors. The indole‐based CUR–BF₂ and CUR compounds and their bis‐thiocyanato derivatives exhibited high anti‐proliferative and apoptotic activity by in vitro bioassays against a panel of 60 cancer cell lines, more specifically against multiple myeloma (MM) cell lines (KMS11, MM1.S, and RPMI‐8226) with significantly lower IC₅₀ values versus healthy PBMC cells; they also exhibited higher anti‐proliferative activity in human colorectal cancer cells (HCT116, HT29, DLD‐1, RKO, SW837, and Caco2) than the parent curcumin, while showing notably lower cytotoxicity in normal colon cells (CCD112CoN and CCD841CoN).     

Dextran-Curcumin Nanosystems Inhibit Cell Growth and Migration Regulating the Epithelial to Mesenchymal Transition in Prostate Cancer Cells

Functional nanocarriers which are able to simultaneously vectorize drugs to the site of interest and exert their own cytotoxic activity represent a significant breakthrough in the search for effective anticancer strategies with fewer side effects than conventional chemotherapeutics. Here, we propose previously developed, self-assembling dextran-curcumin nanoparticles for the treatment of prostate cancer in combination therapy with Doxorubicin (DOXO). Biological effectiveness was investigated by evaluating the cell viability in either cancer and normal cells, reactive oxygen species (ROS) production, apoptotic effect, interference with the cell cycle, and the ability to inhibit cell migration and reverse the epithelial to mesenchymal transition (EMT). The results proved a significant enhancement of curcumin efficiency upon immobilization in nanoparticles: IC₅₀ reduced by a half, induction of apoptotic effect, and improved ROS production (from 67 to 134%) at low concentrations. Nanoparticles guaranteed a pH-dependent DOXO release, with a more efficient release in acidic environments. Finally, a synergistic effect between nanoparticles and Doxorubicin was demonstrated, with the free curcumin showing additive activity. Although in vivo studies are required to support the findings of this study, these preliminary in vitro data can be considered a proof of principle for the design of an effective therapy for prostate cancer treatment.     

Boron and Gadolinium Loaded Fe3O4 Nanocarriers for Potential Application in Neutron Capture Therapy

In this article, a novel method of simultaneous carborane- and gadolinium-containing compounds as efficient agents for neutron capture therapy (NCT) delivery via magnetic nanocarriers is presented. The presence of both Gd and B increases the efficiency of NCT and using nanocarriers enhances selectivity. These factors make NCT not only efficient, but also safe. Superparamagnetic Fe₃O₄ nanoparticles were treated with silane and then the polyelectrolytic layer was formed for further immobilization of NCT agents. Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), energy dispersive X-ray (EDX), ultraviolet–visible (UV-Vis) and Mössbauer spectroscopies, dynamic light scattering (DLS), scanning electron microscopy (SEM), vibrating-sample magnetometry (VSM) were applied for the characterization of the chemical and element composition, structure, morphology and magnetic properties of nanocarriers. The cytotoxicity effect was evaluated on different cell lines: BxPC-3, PC-3 MCF-7, HepG2 and L929, human skin fibroblasts as normal cells. average size of nanoparticles is 110 nm; magnetization at 1T and coercivity is 43.1 emu/g and 8.1, respectively; the amount of B is 0.077 mg/g and the amount of Gd is 0.632 mg/g. Successful immobilization of NCT agents, their low cytotoxicity against normal cells and selective cytotoxicity against cancer cells as well as the superparamagnetic properties of nanocarriers were confirmed by analyses above.     

Miscibility and phase structure of binary blends of polylactide and poly(vinylpyrrolidone)

The miscibility, crystallization behavior, and component interactions of two binary blends, poly(L ‐lactide) (L ‐PLA)/poly(vinylpyrrolidone) (PVP) and poly(D ,L ‐lactide) (DL ‐PLA)/PVP, were studied with differential scanning calorimetry and Fourier transform infrared (FTIR) spectroscopy. The composition‐dependent changes of the glass‐transition temperature (T_g) and degree of crystallinity (X_c) of the L ‐PLA phase indicated that L ‐PLA and PVP were immiscible over the composition range investigated. However, the sharp decrease of X_c with increasing PVP content in the second heating run demonstrated that the cold crystallization process of L ‐PLA was remarkably restricted by PVP. In DL ‐PLA/PVP blends, the existence of two series of isolated T_g's indicated that DL ‐PLA and PVP were phase‐separated, but evidence showed that there was some degree of interaction at the interface of the two phase, especially for the blends with low DL ‐PLA contents. FTIR measurements showed that there was no appreciable change in the spectra of L ‐PLA/PVP with respect to the coaddition of each component spectrum, implying the immiscibility of the two polymers. In contrast to L ‐PLA, the intermolecular interaction between DL ‐PLA and PVP was detected by FTIR; this was evidenced by the observation of a high‐frequency shift of the C?O stretching vibration band of PVP with increasing DL ‐PLA content, which suggested some degree of miscibility. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 88: 973–979, 2003     

Microstructure and Thermomechanical Properties of Glassy Polylactides with Different Optical Purity of the Lactate Units

Microstructure and thermomechanical properties of polylactides (PLA) with different optical purity (OP) of the lactate units were studied in detail. Thermal analysis by DSC revealed that the melting (T_m) and glass transition (T_g) temperatures of PLA can be simulated by the theoretical equations of Flory and Fox, respectively, both decreasing with decreasing OP. The sequential analysis of the PLA samples by ¹³C NMR spectroscopy suggested that the meso‐sequence is more favorably formed than the racemic sequence in the L ‐rich samples. Their glassy specimens made by injection‐moltding showed characteristic behaviors in dynamic mechanical analysis (DMA); the storage modulus (G ′) of the L ‐rich PLA specimens (L ratio = 99.0, 96.1, and 95.8) dropped and subsequently jumped up above T_g correspondingly to the glass‐to‐rubber and rubber‐to‐crystal transitions, respectively. In the G ′ curve of PLA with low L contents (90 and 72.5), only a drop was shown due to the simple glass‐to‐rubber transition. Wide‐angle X‐ray diffraction (WAXD) of the former L ‐rich PLA supported the responsibility of the crystallization for the jump‐up of G ′ above T_g. The tensile strength of these glassy PLA specimens decreased with their decreased OP, while the tensile modulus was almost identical irrespectively of OP. On the other hand, the density of the PLA specimens was inversely proportional to OP, being in contrast to the above T_g change. The opposite relationship between T_g and density changes can reasonably be explained by a packing model in which the partial helices are formed along the L ‐sequenced segments of the PLA chain and randomly packed in solid state to afford a large free volume in between the helices.     

Fabrication of PLA/MWCNT/Fe3O4 composite nanofibers for leukemia cancer cells

The efficient delivery of daunorubicin loaded poly (lactic acid) (PLA)/multiwalled carbon nanotubes (MWCNT)/Fe₃O₄ composite nanofibers was investigated. The synthesized nanofibers were characterized using SEM, TEM, and XRD analysis. The proliferation inhibition effect of PLA/MWCNT/Fe₃O₄ nanofibrous scaffolds on leukemia K562 cell lines was investigated. The effect of nanofiber concentration on the daunorubicin delivery in the absence and presence of external magnetic field was also evaluated. The results indicated that the incorporation of daunorubicin into the prepared nanofibrous scaffold under applied magnetic field could have synergistic cytotoxic effect on leukemia cancer cells. The drug release mechanism followed the non-Fickian transport.     

Epoxy–lignin polyblends. III. Thermal properties and infrared analysis

Differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA) and IR analysis were performed on a nonviscous epoxy polymer system (EP) with Kraft lignin (L) up to 20%. Mixtures of EP with similar amounts of silica (S) as in EP–L polyblends were used as a reference system for the analyses performed. EP–L polyblends cured at room temperature exhibit a single T_g, a fact characteristic for the monophasic systems. One-step tensile storage modulus vs. temperature curves, and related one-peak tensile loss modulus vs. temperature curves were found for all the EP–L polyblends. At about 30°C the tensile storage modulus of EP does not change in the presence of lignin in amounts up to 20% by weight. All these showed that L is miscible with EP and it does not affect the crosslinking at room temperature. IR spectra led to similar conclusions. The gradual decrease of the peak values of tan δ with the amount of L in polyblends is due to an increase in the tensile storage modulus and a decrease of the tensile loss modulus at temperatures close to T_g. This fact is explained by a stronger bond between EP and L, which could be formed at higher temperatures. The DSC and DMA data are in agreement with the mechanical properties of EP–L polyblends, which were reported previously.     

Characterization of biodegradable polymers by inverse gas chromatography. III. Blends of amylopectin and poly(L‐lactide)

The morphology changes and surface thermodynamics of blends of amylopectin (AP)–poly(L ‐lactide) (PLA) were investigated over a wide range of temperatures and compositions using the inverse gas chromatography method. Twenty‐five solutes were selected such as alkanes, acetates, oxy, halogenated, and six‐member ring families. They provided a variety of specific interactions with the blends' surface. The morphology showed two regions, some others showed a de‐polymerization above 130°C. These zones enabled the estimation of T_g and T_m of AP, PLA, and the blends. Blending AP with PLA caused a decrease in AP's T_g value due to the reduction of the degree of crystallinity of the blend. Exothermic values of χ₂₃ were obtained indicating the compatibility of AP and PLA at all temperatures and weight fractions of AP–PLA. The miscibility was favored at 75%AP, only 25%AP–75%PLA composition influenced the degree of crystallinity. The dispersive component of the surface energy of the blends ranged from 16.09 mJ/m² for the pure AP as high as 58.36 mJ/m² at 110°C when AP was mixed with PLA in a 50–50% ratio. The surface energy was at its highest value when the composition was 75% of AP, in good agreement with χ₂₃ values. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

The kinetics of electroreduction of peroxodisulfate anion on electrochemically polished Cd(0 0 0 1) plane

The electroreduction of the peroxodisulfate anion on the electrochemically polished (EP) Cd(0 0 0 1) plane has been studied by cyclic voltammetry and rotating disc electrode methods. The rate constant of the heterogeneous electroreduction reaction of the S₂O₈²⁻ anion on the EP Cd(0 0 0 1) plane dependent on electrode polarisation and base electrolyte concentration has been established. The values of apparent transfer coefficient α_app corrected for the double layer effect, noticeably lower than 0.5 for the EP Cd(0 0 0 1) plane, only very weakly depend on the electrode potential but noticeably on the electrolyte concentration, decreasing with the base electrolyte concentration. The very low values of the apparent charge transfer coefficient show that the activationless charge transfer mechanism is probably valid for EP aqueous solution interface in a good agreement with the theoretical models for the high hydrogen overvoltage metals based on the diabatic charge transfer mechanism from the metal to an ion.     

Mechanical properties and thermal stability of poly(L‐lactide)/calcium carbonate composites

Poly(L ‐lactide) (PLA) was melt‐mixed with micrometer‐sized and nanosized calcium carbonate (CaCO₃) particles before and after modification with calcium stearate. Adhesion between the CaCO₃ particles and the PLA matrix was assessed qualitatively by scanning electron microscopy observation of the fractured surface morphology of the composites. The effect of the incorporation of the CaCO₃ particles on the thermal stability of the PLA‐based composites was quantified by the temperatures corresponding to 5 and 50% of weight loss and the activation energy determined through thermogravimetric analyses of the composites. The tensile strength and modulus values of the composite were improved greatly without a significant loss in the elongation at break when the nanosized CaCO₃ was incorporated up to 30 wt %. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Visible light responsive titanium dioxide–cyclodextrin–fullerene composite with reduced charge recombination and enhanced photocatalytic activity

Titanium dioxide (TiO₂)–fullerene (C₆₀) composite is prepared from TiO₂ and β-cylcodextrin (CD) encapsulated C₆₀ using the solar light irradiation. The absorption of the composite extends to the visible light region due to the charge transfer from CD and C₆₀ to TiO₂. The composite shows reduced charge recombination compared to that of the bare TiO₂ and TiO₂/CD. The rate constant values for the photodegradation reactions of methylene blue and 4-chlorophenol (4-CP) are significantly higher (∼2–5 times) for the composites with 0.5 and 1.5 wt.% C₆₀ compared to that of the bare TiO₂. Photocatalytic studies in the presence of scavengers reveal that the composites produce higher amount of reactive oxygen species (ROS). The enhanced photocatalytic activity of the composites is attributed to the visible light responsiveness, reduced charge recombination and increased formation of ROS. The photodegradation of 4-CP is significantly faster in the presence of the composite with 1.5 wt.% C₆₀ and is attributed to the synergistic effect of higher adsorption and increased ROS formation. The ROS formation by C₆₀ is possible because of the non-aggregated state of C₆₀ molecules in the composite and is assigned to the method which employs CD molecules to disperse C₆₀ in the composite.     

Atorvastatin Modulates the Efficacy of Electroporation and Calcium Electrochemotherapy

Electroporation is influenced by the features of the targeted cell membranes, e.g., the cholesterol content and the surface tension of the membrane. The latter is eventually affected by the organization of actin fibers. Atorvastatin is a statin known to influence both the cholesterol content and the organization of actin. This work analyzes the effects of the latter on the efficacy of electroporation of cancer cells. In addition, herein, electroporation was combined with calcium chloride (CaEP) to assess as well the effects of the statin on the efficacy of electrochemotherapy. Cholesterol-rich cell lines MDA-MB231, DU 145, and A375 underwent (1) 48 h preincubation or (2) direct treatment with 50 nM atorvastatin. We studied the impact of the statin on cholesterol and actin fiber organization and analyzed the cells’ membrane permeability. The viability of cells subjected to PEF (pulsed electric field) treatments and CaEP with 5 mM CaCl₂ was examined. Finally, to assess the safety of the therapy, we analyzed the N-and E-cadherin localization using confocal laser microscopy. The results of our investigation revealed that depending on the cell line, atorvastatin preincubation decreases the total cholesterol in the steroidogenic cells and induces reorganization of actin nearby the cell membrane. Under low voltage PEFs, actin reorganization is responsible for the increase in the electroporation threshold. However, when subject to high voltage PEF, the lipid composition of the cell membrane becomes the regulatory factor. Namely, preincubation with atorvastatin reduces the cytotoxic effect of low voltage pulses and enhances the cytotoxicity and cellular changes induced by high voltage pulses. The study confirms that the surface tension regulates of membrane permeability under low voltage PEF treatment. Accordingly, to reduce the unfavorable effects of preincubation with atorvastatin, electroporation of steroidogenic cells should be performed at high voltage and combined with a calcium supply.     

Microstructure and Thermal Properties of Polylactides with Different L‐ and D‐Unit Sequences: Importance of the Helical Nature of the L‐Sequenced Segments

A series of polylactides (PLA) with different stereo sequences are prepared by the copolymerization of L ‐lactide and DL ‐lactide. It is confirmed that the glass transition temperature (T_g) of the PLA decreases with decreasing optical purity of the lactate units (%ee) according to the Fox's equation. Analysis of the FT‐IR spectra of these PLA samples reveals that the absorbance at 1 265 cm^?1 (δCH + νCOC) decreases with increasing L ‐content while the absorbance at 1 210 cm^?1 (ν_asCOC + r_asCH₃) increases with increasing L ‐content. These changes in absorbance are reasonably correlated with the randomness and helical nature of the L ‐sequenced segments involved in PLA. Namely, the PLA chains with higher L ‐content comprise a higher number of short helical blocks that are made of several L ‐lactate units. This difference in helical nature causes the opposite dependences of T_g and density on the L ‐content of PLA; i.e., the increased T_g and decreased density with increasing L ‐content.

FT‐IR spectra of a PDLLA film, NO‐PLLA, and BO‐PLLA.     

Mechanical,thermal, and morphology properties of poly(lactic acid) plasticized with poly(ethylene glycol) and epoxidized palm oil hybrid plasticizer

Poly(lactic acid) (PLA) has received great attention recently due to its good physical and mechanical properties such as high tensile strength and modulus, good processability and biodegradability. In this study, low molecular weight poly(ethylene glycol) (PEG) and epoxidized palm oil (EPO) were used as hybrid plasticizers to improve toughness and ductility of PLA. Using the solubility parameter, a tentative evaluation of the hybrid plasticizer that could act as the most effective plasticizer for PLA has been performed and the obtained results have been corroborated with the materials physical properties. Excellent plasticizing effect was obtained by hybrid plasticizer PEG:EPO with ratio 2:1. Addition of PEG:EPO (2:1) hybrid plasticizer to PLA shows a significant improvement of 12,402%, compared to neat PLA. The improvement in flexibility and decrease in rigidity for the plasticized PLA is well evidenced by lower glass transition temperature (T_g) and tensile modulus values. In relation to the thermal stability, a decrease in thermal properties of the hybrid plasticized PLA was observed due to the volatility of the plasticizers. Scanning electron microscopy (SEM) shows that the hybrid plasticizer was turned PLA's smooth surface to fibrous structure and rough fracture surface. POLYM. ENG. SCI., 56:1169–1174, 2016. © 2016 Society of Plastics Engineers     

Terpolymers from lactide and bisphenol a derivatives: Scale‐up,properties, and blends

Terpolymerization of L‐lactide (LA) and bisphenol A derivatives was performed on few hundred gram scale, and the resultant terpolymer (TP) was characterized by gel permeation chromatography, infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA), and thermogravimetric analysis. Moderate molecular weight (M_n ～ 12 kg/mol) TP was achieved with glass transition temperatures about 100°C (DSC and DMA). The TP exhibited improved thermal stability compared with polylactide (PLA), with a thermal degradation temperature of about 80°C higher than PLA. Although the TP exhibited distinctly different surface morphology compared with that of PLA, both showed similar contact angle and surface energy (ca. 40 mN/m) properties. Blends of PLA and TP showed enhanced glass transition (～ 5°C change in T_g) temperatures compared with PLA homopolymer. This is due to the compatibility of PLA and TP. Thus, TP could be used as an additive for PLA‐based blends to enhance compatibility with phenolic‐based resins. TP electrospun fiber morphology is also reported. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Biodegradable Tri-Block Copolymer Poly(lactic acid)-poly(ethylene glycol)-poly(l-lysine)(PLA-PEG-PLL) as a Non-Viral Vector to Enhance Gene Transfection

Low cytotoxicity and high gene transfection efficiency are critical issues in designing current non-viral gene delivery vectors. The purpose of the present work was to synthesize the novel biodegradable poly (lactic acid)-poly(ethylene glycol)-poly(l-lysine) (PLA-PEG-PLL) copolymer, and explore its applicability and feasibility as a non-viral vector for gene transport. PLA-PEG-PLL was obtained by the ring-opening polymerization of Lys(Z)-NCA onto amine-terminated NH₂-PEG-PLA, then acidolysis to remove benzyloxycarbonyl. The tri-block copolymer PLA-PEG-PLL combined the characters of cationic polymer PLL, PLA and PEG: the self-assembled nanoparticles (NPs) possessed a PEG loop structure to increase the stability, hydrophobic PLA segments as the core, and the primary ɛ-amine groups of lysine in PLL to electrostatically interact with negatively charged phosphate groups of DNA to deposit with the PLA core. The physicochemical properties (morphology, particle size and surface charge) and the biological properties (protection from nuclease degradation, plasma stability, in vitro cytotoxicity, and in vitro transfection ability in HeLa and HepG2 cells) of the gene-loaded PLA-PEG-PLL nanoparticles (PLA-PEG-PLL NPs) were evaluated, respectively. Agarose gel electrophoresis assay confirmed that the PLA-PEG-PLL NPs could condense DNA thoroughly and protect DNA from nuclease degradation. Initial experiments showed that PLA-PEG-PLL NPs/DNA complexes exhibited almost no toxicity and higher gene expression (up to 21.64% in HepG2 cells and 31.63% in HeLa cells) than PEI/DNA complexes (14.01% and 24.22%). These results revealed that the biodegradable tri-block copolymer PLA-PEG-PLL might be a very attractive candidate as a non-viral vector and might alleviate the drawbacks of the conventional cationic vectors/DNA complexes for gene delivery in vivo.     

Fabrication of superhydrophobic polylactide films with ultraviolet-shielding properties

ZnO is a useful material with stable physical and chemical properties for introducing surface roughness and UV-blocking properties. However, to inhibit ZnO particles’ photocatalytic degradation of peripheral organic materials, we conducted layer-by-layer (LbL) deposition with poly(sodium 4-styrenesulfonate) and poly(diallyl dimethyl ammonium chloride) to fabricate ZnO particles with an SiO₂ shell with tetraethyl orthosilicate. Polylactide (PLA) films were prepared by compression molding and treated with a weak alkali solution for 0.5, 1.0, 1.5, and 2.0 h to induce hydroxyl and carboxyl groups. The LbL deposition of polyelectrolytes on the PLA film was performed to induce electrical interactions between the PLA films and ZnO composite particles. ZnO composite particles were deposited onto the surface of the PLA films with dip coating, and a stable superhydrophobic surface was developed after hexadecyl trimethoxysilane treatment via a reduction in the surface energy. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 47760.     

Incomptine A Induces Apoptosis,ROS Production and a Differential Protein Expression on Non-Hodgkin’s Lymphoma Cells

Sesquiterpene lactones are of pharmaceutical interest due their cytotoxic and antitumor properties, which are commonly found within plants of several genera from the Asteraceae family such as the Decachaeta genus. From Decachaeta incompta four heliangolide, namely incomptines A-D have been isolated. In this study, cytotoxic properties of incomptine A (IA) were evaluated on four lymphoma cancer cell lines: U-937, Farage, SU-DHL-2, and REC-1. The type of cell death induced by IA and its effects on U-937 cells were analyzed based on its capability to induce apoptosis and produce reactive oxygen species (ROS) through flow cytometry with 4′,6-diamidino-2-phenylindole staining, dual annexin V/DAPI staining, and dichlorofluorescein 2′,7′-diacetate, respectively. A differential protein expression analysis study was carried out by isobaric tags for relative and absolute quantitation (iTRAQ) through UPLC-MS/MS. Results reveal that IA exhibited cytotoxic activity against the cell line U-937 (CC₅₀ of 0.12 ± 0.02 μM) and the incubation of these cells in presence of IA significantly increased apoptotic population and intracellular ROS levels. In the proteomic approach 1548 proteins were differentially expressed, out of which 587 exhibited a fold-change ≥ 1.5 and 961 a fold-change ≤ 0.67. Most of these differentially regulated proteins are involved in apoptosis, oxidative stress, glycolytic metabolism, or cytoskeleton structuration.