Copper Transfer from Cu–Aβ to Human Serum Albumin Inhibits Aggregation,Radical Production and Reduces Aβ Toxicity

Amyloid‐β peptides (Aβ) and the protein human serum albumin (HSA) interact in vivo. They are both localised in the blood plasma and in the cerebrospinal fluid. Among other functions, HSA is involved in the transport of the essential metal copper. Complexes between Aβ and copper ions have been proposed to be an aberrant interaction implicated in the development of Alzheimer's disease, where Cu is involved in Aβ aggregation and production of reactive oxygen species (ROS). In the present work, we studied copper‐exchange reaction between Aβ and HSA or the tetrapeptide DAHK (N‐terminal Cu‐binding domain of HSA) and the consequence of this exchange on Aβ‐induced ROS production and cell toxicity. The following results were obtained: 1) HSA and DAHK removed Cu^II from Aβ rapidly and stoichiometrically, 2) HSA and DAHK were able to decrease Cu‐induced aggregation of Aβ, 3) HSA and DAHK suppressed the catalytic HO^. production in vitro and ROS production in neuroblastoma cells generated by Cu–Aβ and ascorbate, 4) HSA and DAHK were able to rescue these cells from the toxicity of Cu–Aβ with ascorbate, 5) DAHK was more potent in ROS suppression and restoration of neuroblastoma cell viability than HSA, in correlation with an easier reduction of Cu^II–HSA than Cu–DAHK by ascorbate, in vitro. Our data suggest that HSA is able to decrease aberrant Cu^II–Aβ interaction. The repercussion of the competition between HSA and Aβ to bind Cu in the blood and brain and its relation to Alzheimer's disease are discussed.     

Hollow mesoporous silica capsules loaded with copper,silver, and zinc oxide nanoclusters for sustained antibacterial efficacy

Intensive and overuse of antibiotics during the last years has triggered a distinct rise in antibiotic resistance worldwide. In addition to the newly developed antimicrobials, there is a high demand for alternative treatment options against persistent bacterial infections. The biocidal impact of metal ions like copper (Cu²⁺), silver (Ag⁺), and zinc (Zn²⁺), also known as the oligodynamic effect has been used for ages to kill or inhibit the growth of microorganisms and to employ long-term prevention strategies against their biological antagonists. Herein, we report on the synthesis of Cu, Ag, and Zn metal and corresponding oxide nanoparticles immobilized on hollow mesoporous silica capsules (HMSCs) obtained by a hard-template assisted sol-gel synthesis followed by reduction of appropriate metal salts in the presence of HMSCs. Compartmentalization of nanosized metal and oxide clusters in Ag@HMSCs, Cu@HMSCs, and ZnO@HMSCs particles prevented their agglomeration and offered high release kinetics of metal ions between 2.0 and 3.7 mM during 24 h, as monitored by UV-vis analyses. The distribution and morphology of pristine and metal functionalized HMSCs were evaluated by transmission electron microscopy analysis revealing the successful synthesis of Ag, Cu, and ZnO nanoparticles supported on HMSCs. X-ray photoelectron spectroscopy revealed that mainly Cu(II), Ag(0), and Zn(II) species were present in the modified HMSCs. In addition to the surface attachment of preformed metal (Ag and Cu) and metal oxide (ZnO) cluster, nucleation of metal nanoparticles inside the void of HMSCs provided an internal reservoir which allowed for a time-dependent release of metal ions through slower dissolution rates leading to a long-term and sustained bacterial inhibition over several hours. The high antimicrobial efficiency of Ag@HMSCs, Cu@HMSCs, and ZnO@HMSCs particles was investigated toward both Gram-positive (Bacillus subtilis) and Gram-negative (Escherichia coli) bacteria by INT assays showing a complete growth inhibition for both bacteria types after 24 h. While Ag@HMSCs and Cu@HMSCs showed a higher susceptibility against Gram-negative bacteria, ZnO@HMSCs showed a higher susceptibility against Gram-positive bacteria. This demonstrates the promise of metal-loaded capsules as antibacterial delivery vehicles with dual-mode time-release profiles being potential alternatives for antibiotic drugs.     

Tuned interactions of silver nanoparticles with ZSM-5 zeolite by adhesion-promoting poly(acrylic acid) deposited by electrospray ionization (ESI)

The electrospray ionization (ESI) method was used for deposition of thin films of poly(acrylic acid) (PAA) on Cu/ZSM-5 (5 wt.% Cu) and Ag–Cu/ZSM-5 (1 wt.% Ag and 4 wt.% Cu) composites. For comparative purposes, the ZSM-5 zeolite was synthesized under hydrothermal conditions and loaded with PAA under the same treating conditions as the composites. This method allowed the formation of uniform polymer films of controlled thickness on conductive substrates. The structural characteristics were characterized by X-ray photoelectron spectroscopy, Fourier-transform infrared spectroscopy, atomic force microscopy and X-ray diffraction (XRD). The deposited PAA layer over ZSM-5 acts as a common dispersing and stabilizing agent through coordination-driven guest-templated polymer via interaction of Ag⁺ and Cu²⁺ with carboxylic acid groups, thus increasing and controlling the adhesion and the release of metallic species. A short exposure to light and temperature has reduced the metal ions to Cu⁰ and Ag⁰ metallic nanoparticles. The results of XRD analysis let suggest that the interaction of Cu and Ag with carboxylic groups of PAA inhibits the formation of large metallic silver particles. These samples were being studied for their potential as antibacterial agents toward the bacterial strains such as Staphylococcus pneumonia, Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa as Gram positive and Gram negative bacteria, respectively. Aspergillus fumigatus and Candida albicans as Fungi were also evaluated. The Cu/ZSM-5 and Ag–Cu/ZSM-5 nanocomposites coated with a 10 nm thick PAA layer exhibit significant antibacterial activity.     

Aptamer-Aptamer Chimera for Targeted Delivery and ATP-Responsive Release of Doxorubicin into Cancer Cells

Aptamers offer a great opportunity to develop innovative drug delivery systems that can deliver cargos specifically into targeted cells. In this study, a chimera consisting of two aptamers was developed to deliver doxorubicin into cancer cells and release the drug in cytoplasm in response to adenosine-5′-triphosphate (ATP) binding. The chimera was composed of the AS1411 anti-nucleolin aptamer for cancer cell targeting and the ATP aptamer for loading and triggering the release of doxorubicin in cells. The chimera was first produced by hybridizing the ATP aptamer with its complementary DNA sequence, which is linked with the AS1411 aptamer via a poly-thymine linker. Doxorubicin was then loaded inside the hybridized DNA region of the chimera. Our results show that the AS1411–ATP aptamer chimera was able to release loaded doxorubicin in cells in response to ATP. In addition, selective uptake of the chimera into cancer cells was demonstrated using flow cytometry. Furthermore, confocal laser scanning microscopy showed the successful delivery of the doxorubicin loaded in chimeras to the nuclei of targeted cells. Moreover, the doxorubicin-loaded chimeras effectively inhibited the growth of cancer cell lines and reduced the cytotoxic effect on the normal cells. Overall, the results of this study show that the AS1411–ATP aptamer chimera could be used as an innovative approach for the selective delivery of doxorubicin to cancer cells, which may improve the therapeutic potency and decrease the off-target cytotoxicity of doxorubicin.     

Isolation and dispersion of reduced metal particles using the surface dipole moment of F-terminated diamond electrodes

Cu particles that have been reductively generated at the oxidized surface of a boron-doped diamond electrode (O-BDD) can be removed from the electrode's surface by the repulsive electrostatic force of the surface dipole moment during a potential cycle of a solution of Cu²⁺ ions. The objective of this study was to isolate various metal particles other than Cu by use of a fluorine-terminated BDD surface (F-BDD) with a stronger surface dipole moment than O-BDD, and to clarify the mechanism of the metal particles’ separation from the electrode.During the potential cycle treatment of Cu²⁺ ions using F-BDD, the reionization of the reduced Cu could be suppressed in the presence of dissolved oxygen, and the Cu particles were separated from the electrode surface as CuO. A similar result was seen with O-BDD. The degree of separation of the Cu particles could be drastically enhanced by raising the upper potential limit in the potential cycle from +0.2 to +0.8 V. By setting the upper potential to a potential greater than the metal-metal oxide equilibrium line in the potential-pH equilibrium diagram of the Cu-water system (Pourbaix Diagram), oxidation of the reduced metal surface by reaction with dissolved oxygen could be accelerated and the surface of metal particles could be insulated. The Cu particles were forced from the BDD surface by the electrostatic repulsion from the surface dipole moment of F-BDD. Also, it turned out that the physical adsorption of chloride ions (Cl⁻) on the electrode surface intensified the electrostatic repulsive force between the F- or O-BDD surface and the metal particles, and thus increased the degree of the metal particles’ separation.For Zn with a metal-metal oxide equilibrium potential of approximately −0.8 V at pH 7, complete separation of the Zn particles was achieved with F-BDD by setting the upper potential limit to +0.8 V (vs. Ag/AgCl), decreasing the Zn²⁺ concentration (1/10 that of Cu²⁺) and optimizing the sweep rate to minimize the Zn particle diameter. This result was hard to achieve with O-BDD. The separation of metal particles other than Cu was achieved with F-BDD because of its stronger surface dipole moment. However, with noble type metals (such as Pt and Ni) that have metal-metal oxide equilibrium potentials higher than the upper potential limit for potential cycling with F-BDD (+0.8 V), the surfaces of the reduced metal particles were not insulated and metal particles were deposited on the BDD surface. In order to isolate metal particles from the electrode, it was necessary to apply a maximum potential over that of the metal-metal oxide equilibrium line in the Pourbaix Diagram during the potential cycle.     

Steam Reforming of Methanol Over Cu/CeO2 Catalysts Studied in Comparison with Cu/ZnO and Cu/Zn(Al)O Catalysts

A series of Ce_1-xCu_xO_2- mixed oxides were synthesized using a co-precipitation method and tested as catalysts for the steam reforming of methanol. XRD patterns of the Ce_1-xCu_xO_2- mixed oxides indicated that Cu²⁺ ions were dissolved in CeO₂ lattices to form a solid solution by calcination at 773K when x < 0.2. A TPR (temperature-programmed reduction) investigation showed that the CeO₂ promotes the reduction of the Cu²⁺ species. Two reduction peaks were observed in the TPR profiles, which suggested that there were two different Cu²⁺ species in the Ce_1-xCu_xO_2- mixed oxides. The TPR peak at low temperature is attributed to the bulk Cu²⁺ species which dissolved into the CeO₂ lattices, and the peak at high temperature is due to the CuO species dispersed on the surface of CeO₂. The Ce_1-xCu_xO_2- mixed oxides were reduced to form Cu/CeO₂ catalysts for steam reforming of methanol, and were compared with Cu/ZnO, Cu/Zn(Al)O and Cu/AL₂O₃ catalysts. All the Cu-containing catalysts tested in this study showed high selectivities to CO₂ (over 97%) and H₂. A 3.8wt% Cu/CeO₂ catalyst showed a conversion of 53.9% for the steam reforming of methanol at 513K (W/F = 4.9 g h mol^-1), which was higher than that over Cu/ZnO (37.9%), Cu/Zn(Al)O (32.3%) and Cu/AL₂O₃ (11.2%) with the same Cu loading under the same reaction conditions. It is likely that the high activity of the Cu/CeO₂ catalysts may be due to the highly dispersed Cu metal particles and the strong metalsupport interaction between the Cu metal and CeO₂ support. Slow deactivations were observed over the 3.8wt% Cu/CeO₂ catalyst at 493 and 513K. The activity of the deactivated catalysts can be regenerated by calcination in air at 773K followed by reduction in H₂ at 673K, which indicated that a carbonaceous deposit on the catalyst surface caused the catalyst deactivation. Using the TPO (temperature-programmed oxidation) method, the amounts of coke on the 3.8wt% Cu/CeO₂ catalyst were 0.8wt% at 493K and 1.7wt% at 513K after 24h on stream.     

Copper Biosorption on Magnetically Modified Yeast Cells Under Magnetic Field

Brewer's yeast (bottom yeast, Saccharomyces cerevisiae subsp. uvarum) cells were magnetically modified using water-based magnetic fluid stabilized perchloric acid. The magnetically modified yeast cells were characterized by scanning electron microscopy (SEM). Cu²⁺ biosorption properties of magnetically modified yeast cells from synthetic solutions were utilized in a continuous magnetic system. The Cu²⁺ ion-binding capacity decreased drastically with the increase of the flow rate. The maximum Cu²⁺ biosorption capacity was obtained to be 1.2 mmol/g at 25°C. Biosorption of Cu²⁺ increased with increasing pH and then reached almost a plateau value around pH 4.0. The yeast biomass can be easily regenerated by 0.1 M HNO₃ with higher effectiveness. Biosorption of heavy metal ions from artificial wastewater was also studied. The biosorption capacities are 0.92 mmol/g for Cu²⁺, 0.52 mmol/g for Hg²⁺, and 0.28 mmol/g for Ni²⁺. Magnetically-modified yeast cells exhibits the following metal ion-affinity sequence: Cu²⁺ > Hg²⁺ > Ni²⁺.     

Poly(4‐vinyl pyridine)‐grafted graphene oxide for drug delivery and antimicrobial applications

Graphene oxide (GO) was covalently functionalized with poly(4‐vinyl pyridine) (P4VP) by atom transfer radical polymerization for drug delivery and antimicrobial applications. The physiochemical properties, chemical structure, composition and morphology of the P4VP‐functionalized GO (GO‐P4VP) were studied. Simple physisorption of a cancer drug, camptothecin (CPT), via π ? π stacking and/or hydrophobic interactions on the GO‐P4VP was tested for drug loading and its release by altering the pH. The GO‐P4VP has low cytotoxicity, and the CPT‐loaded GO‐P4VP exhibited a high potency for killing cancer cells in vitro. Prominent antimicrobial properties against Escherichia coli and Staphylococcus aureus were also observed. Thus, the GO‐P4VP can be utilized as a drug delivery vector with high biocompatibility, solubility and stability in physiological solutions, a suitable payload capacity and excellent bacterial toxicity. Owing to its small size, low cost, large specific area, ready scalability and useful non‐covalent interactions, GO‐P4VP is a novel material for biomedical, industrial and environmental applications. © 2015 Society of Chemical Industry     

pH sensitive functionalized hyperbranched polyester based nanoparticulate system for the receptor-mediated targeted cancer therapy

The aim of this study is to develop a novel folic acid conjugated, DL-lysine modified, PEGylated, the 3rd generation hyperbranched polymer (HBP-PEG-Lys-FA) for use in receptor-mediated therapy. 5-fluorouracil, model anti-cancer drug, loaded nanoparticles were found an average size of 177?nm with loading efficiency of 23.18%. In vitro drug release studies demonstrated that nanoparticles showed pH-dependent release. HBP-PEG-Lys-FA were efficiently taken up by HeLa cells and specificity of targeted nanoparticles to folate receptors of cells was proved. It was concluded that the HBP-PEG-Lys-FA nanoparticles can provide an advantage on delivering of the drug efficiently into the cytosol for cancer therapy.     

Polymer assisted ultrafiltration for copper–citric acid chelate removal from wash solutions of contaminated soil

The removal of heavy metals from aqueous systems such as wash-solutions of contaminated soil by using Polymer-Assisted Ultrafiltration (PAUF) has been studied. For the extraction of metal ions from contaminated soil citric acid is used as a chelating agent. Cu²⁺ as metal ion and the polymer polyethylenimine (PEI) as ligand were used in the various experiments. Optimal chemical conditions for copper complexation by citric acid were determined by means of complexation tests. The results showed that citric acid is able to chelate copper ions at pH 5.5, while decomplexation occurs at pH 2. Maximum bonding capacity (saturation condition) was 0.625 mg Cu²⁺ per mg citric acid, meaning 2 mol Cu²⁺ per mol citric acid. Complexation tests in the system polyethylenimine–citric acid–copper showed that the polymer is able to complex the copper–citric acid chelate at pH = 6 while release occurs at pH < 3. The saturation condition was 0.333 mg Cu²⁺ per mg PEI. The ultrafiltration tests, carried out at three trans-membrane pressures (2, 3 and 4 bar), showed the possibility of using the PAUF technique for copper ion removal from aqueous solutions.     

An investigation into transition metal ion binding properties of silk fibers and particles using radioisotopes

Silk is a structural protein fiber that is stable over a wide pH range making it attractive for use in medical and environmental applications. Variation in amino acid composition has the potential for selective binding for ions under varying conditions. Here we report on the metal ion separation potential of Mulberry and Eri silk fibers and powders over a range of pH. Highly sensitive radiotracer probes, ⁶⁴Cu²⁺, ¹⁰⁹Cd²⁺, and ⁵⁷Co²⁺ were used to study the absorption of their respective stable metal ions Cu²⁺, Cd²⁺, and Co²⁺ into and from the silk sorbents. The total amount of each metal ion absorbed and time taken to reach equilibrium occurred in the following order: Cu²⁺ > Cd²⁺ > Co²⁺. In all cases the silk powders absorbed metal ions faster than their respective silk fibers. Intensive degumming of the fibers and powders significantly reduced the time to absorb respective metal ions and the time to reach equilibrium was reduced from hours to 5–15 min at pH 8. Once bound, 45–100% of the metal ions were released from the sorbents after exposure to pH 3 buffer for 30 min. The transition metal ion loading capacity for the silk sorbents was considerably higher than that found for commercial ion exchange resins (AG MP‐50 and AG 50W‐X2) under similar conditions. Interestingly, total Cu²⁺ bound was found to be higher than theoretically predicted values based on known specific Cu²⁺ binding sites (AHGGYSGY), suggesting that additional (new) sites for transition metal ion binding sites are present in silk fibers. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Biocompatible tumor micro-environment responsive CS-g-PNIPAAm co-polymeric nanoparticles for targeted Oxaliplatin delivery

The objective of the research study was to develop and characterize a biodegradable, thermo and pH dual responsive Oxaliplatin-loaded chitosan-graft-poly-N-isopropylacrylamide (CS-g-PNIPAAm) co-polymeric nanoparticles as a tumor-targeting drug delivery system. CS-g-PNIPAAm co-polymers were synthesized, characterized and optimized its thermo and pH responsive properties for tumor microenvironment conditions. Optimized co-polymer could be efficiently loaded with Oxaliplatin in nanoparticle form, evaluated for their morphology (TEM), particle size, zeta potential, loading efficiency and drug content. In vitro drug release study at tumor microenvironment and physiological pH and temperature conditions. The in vitro drug release was optimal at above lower critical solution temperature (LCST) and tumor microenvironment pH when compared to physiological pH & temperature. MTT assay and fluorescence microscopic study showed that drug release and cell uptake was significantly enhanced in tumor microenvironment. In conclusion, the obtained nanoparticles appeared to be of great promise in tumor targeted drug delivery of oxaliplatin.     

Novel heterogeneous photocatalysts prepared with waste wool and Fe3+ or Cu2+ ions for degradation of CI Reactive Red 195: a comparative study

In order to reuse waste wool, two transition metal ions, Fe³⁺ and Cu²⁺, were coordinated to with it to prepare a series of metal–wool complexes as new heterogeneous Fenton photocatalysts for the degradation of a typical azo dye, CI Reactive Red 195, in aqueous solution. The effect of the initial metal ion concentration and temperature on the reaction was investigated. Furthermore, the catalytic performance of the resulting metal–wool complexes was evaluated with respect to the dye decoloration efficiency at different pH levels under visible irradiation. The results demonstrated that increasing the initial metal ion concentration and temperature enhanced ion coordination to produce complexes of increased metal content. The obtained Fe–wool showed a higher metal content than the Cu–wool. The light adsorption performance in the UV and visible regions of Cu–Fe–wool is stronger than that of Fe–wool or Cu–wool. Furthermore, Cu–Fe–Wool was found to have a higher catalytic activity than the other two complexes under visible irradiation, especially in the alkaline pH range.     

Metal ion binding properties of novel wool powders

Wool fibres have shown potential for the removal and recovery of toxic chemical and metal ions; however, their slow kinetics of binding has limited their widespread application. In this study three wool powders have been prepared from chopped wool fibre using various milling operations. Brunauer, Emmett, Teller analysis (BET) showed negligible change in surface area and Positron annihilation lifetime spectroscopy indicated no change in nanoporosity of the powders on processing. Binding of the transition metal ions, Co²⁺, Cu²⁺, and Cd²⁺ was investigated over the pH range 3–9 at ambient temperature (23°C) using their respective radioisotopes (i.e. ⁵⁷Co, ⁶⁴Cu, or ¹⁰⁹Cd). The optimum pH for binding of Cu²⁺ and Cd²⁺ was in the range 6–8, while Co²⁺ absorption peak was sharp at pH 8. The rate of uptake of Cu²⁺ for each of the wool powder was dramatically faster (～ 42 fold) than that of the wool fibre. In comparison with commercial cation exchange resins, the wool powders showed significantly higher (two to nine fold) metal ion loading capacity. Selective binding of the metal ions could be enhanced by varying pH and/or incubation times. The use of radioisotopes to monitor the metal ion binding allowed the development of a highly sensitive and rapid high‐throughput analysis method for assessing wool powder binding properties. The ability to produce large quantities of wool powders and their ease of handling indicate that they have potential for application in separation and recovery of metal ions from industrial effluents and environmental waterways. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Fabrication of polymer/drug‐loaded hydroxyapatite particle composite fibers for drug sustained release

The aim of this study is to fabricate polymer/hydroxyapatite (HA) particle composite fibers for drug encapsulation and sustained release. Firstly, drug‐loaded hydroxyapatite particles are synthesized in one step, then by electrospinning of the blends of drug‐loaded hydroxyapatite particles and polymer solution the drug‐loaded polymer/hydroxyapatite particle composite fibers are successfully prepared. Effect of loading ratio of drug‐loaded hydroxyapatite particles in the fibers and pH value of the release medium on the drug release kinetics are both investigated, and the results demonstrate that, as compared with the polymer/drug electrospun fibers, the drug in the polymer/drug‐loaded hydroxyapatite particle composite fibers shows a sustained release manner, and the drug release rate can be regulated by both the loading ratio of drug‐loaded hydroxyapatite particles in the composite fibers and pH value of the buffer solution. The results indicate that the developed drug‐loaded polymer/hydroxyapatite particle composite fibers show great potential in bone regeneration and other related biomedical fields. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 42871.     

Redox and pH dual-responsive biodegradable mesoporous silica nanoparticle as a potential drug carrier for synergistic cancer therapy

Multifunctional mesoporous silica-based nanocarriers able to efficiently encapsulate drugs for stimuli-responsive release and display rapid biodegradation are highly desirable. In this work, we dope disulfide bonds and calcium into silica framework by one step method to obtain a redox and pH dual-responsive biodegradable mesoporous silica nanoparticle (BT-Ca-MSN) as a potential drug carrier for synergistic cancer therapy. TEM and ICP-OES are used to assess the biodegradation behavior of BT-Ca-MSN. The results show that BT-Ca-MSN can significantly biodegrade in a concurrent reductive and acidic environment due to the simultaneous disulfide bonds cleavage and Ca²⁺ release. In addition, BT-Ca-MSN shows efficient drug loading capacity and significant biodegradation-mediated drug release. Moreover, the in-vitro cytotoxicity indicates that BT-Ca-MSN can not only exhibit significant cancer cell killing effect without obvious toxicity on healthy cells via the way of released Ca²⁺-mediated apoptosis, but also can combine with its loaded doxorubicin hydrochloride for synergistic cancer therapy. This work demonstrates that BT-Ca-MSN is a promising platform as drug carrier, providing a paradigm to rationally design biodegradable silica-based carriers for highly efficient cancer therapy.     

Hollow Mesoporous Silica@Metal–Organic Framework and Applications for pH‐Responsive Drug Delivery

Metal?‐organic frameworks (MOFs), a new type of porous crystalline material, hold great potential in biomedical applications, such as drug delivery. However, the efficacy of drug delivery is limited by low drug loading. In this work, we synthesized hollow mesoporous silica (HMS)@MOF capsules that can be used as a pH‐responsive drug delivery system for the anticancer drug doxorubicin (DOX). DOX is loaded into the inner cavity of HMS. Zeolitic imidazolate framework‐8 (ZIF‐8) nanoparticles are then coated on the outer surface of the DOX‐loaded HMS. The obtained material is a capsule (denoted as DOX/HMS@ZIF), in which DOX is encapsulated. The DOX/HMS@ZIF can be used as an efficient pH‐responsive drug delivery system. DOX is not released under physiological conditions (pH 7.4), but is released at low pH (4–6) from DOX/HMS@ZIF. The DOX/HMS@ZIF capsule shows much higher cytotoxicity than free DOX and alters the delivery pathway for DOX in cancer cells, while the drug‐free HMS@ZIF shows excellent biocompatibility. This opens new opportunities to construct a safe and efficient delivery system for targeted molecules using pH‐responsive release for a wide range of applications.     

Intracellular pH‐sensitive dextran‐based micelles as efficient drug delivery platforms

As drug delivery systems, stimuli‐responsive polymer micelles hold great potential in cancer chemotherapeutics to improve therapeutic efficiency and eliminate organism adverse effects. Here, pH‐sensitive polymeric micelles based on dextran‐g‐benzimidazole were designed and used for intracellular anticancer drug delivery. The anticancer drug doxorubicin (DOX) was effectively loaded into the micelles via hydrophobic interactions. In vitro release studies demonstrated that the release of loaded DOX was greater and faster under acid conditions such as in carcinomatous areas (pH < 6.8) than in physiological conditions (pH 7.4). MTT assays and flow cytometric analyses showed that DOX‐loaded micelles had higher cellular proliferation inhibition towards HeLa and HepG2 cells than pH‐insensitive controls. These pH‐sensitive micelles with significant efficiency for intracellular drug release will be beneficial to the future of in vivo biomedical applications. © 2014 Society of Chemical Industry     

Selective Recovery of Copper,Cobalt, and Nickel from Aqueous Chloride Media using Solvent Impregnated Resins

Selective recovery of copper, cobalt, and nickel from acidic chloride media was investigated with solvent impregnated resins (SIRs) containing acidic organophosphorus extractants. The adsorption of each metal with the SIR proceeds via a cation exchange mechanism. An SIR containing 2-ethylhexylphosphonic acid mono-2-ethylhexyl ester (PC-88A) has high selectivity for Cu²⁺, and the order of selectivity is Cu²⁺ > Co²⁺ > Ni²⁺. Effective adsorption-elution can be achieved by chromatographic operation for the selective recovery of Cu²⁺ from a ternary metal solution. High selectivity for Co²⁺ was observed using a SIR comprising bis-2,4,4-trimethylpentylphosphinic acid (Cyanex 272) and can be effectively separated from a Co and Ni binary metal solution by column adsorption. A simple and effective process flow sheet is proposed for selective recovery of Cu²⁺, Co²⁺, and Ni²⁺ from aqueous chloride media using the two SIRs.     

Surfactant free-poly(lactic-co-glycolic acid) coated artesunate loaded citrate-functionalized hydroxyapatite nanorods as a nanocapsule for improving artesunate delivery and antitumor efficiency

The development of targeted drug delivery systems with controlled drug release and enhanced drug bioavailability has attracted increasing attention as a candidate for clinical applications. We designed biocompatible citrate-functionalized hydroxyapatite nanorods (Cit-HAp NRs) loaded with artesunate (ART) for use in colon cancer therapies. These were then encapsulated into surfactant free PLGA nanoparticles (ART@Cit-HAp NRs/SF-PLGA NPs). The synthesized Cit-HAp NRs, ART-loaded Cit-HAp NRs and ART@Cit-HAp NRs/SF-PLGA NPs were characterized using a variety of comprehensive techniques. An ART loading efficiency of ～92% was observed upon using a 1:10 mass ratio (ART: Cit-HAp NRs). We revealed that the adsorption of ART on Cit-HAp NRs proceeds via a pseudo-second-order adsorption mechanism. The in vitro ART release from the nanocomposites (ART@Cit-HAp NRs/SF-PLGA NPs) exhibits a pH dependent release and the rate of ART release from the ART@Cit-HAp NRs/SF-PLGA NPs was slower than the release from Cit-HAp NRs. The effects of ART@Cit-HAp NRs/SF-PLGA NPs were evaluated in human colon cancer (HCT 116 and Caco-2) cell lines. ART@Cit-HAp NRs/SF-PLGA NPs demonstrated higher anti-proliferation activity compared with free ART. The delivery of ART using Citrate-functionalized hydroxyapatite encapsulated, surfactant free PLGA nanoparticles as a carrier could improve their anti-cancer activities.