Luying Wang

Self-assembled targeted nanoparticles based on transferrin-modified eight-arm-polyethylene glycol–dihydroartemisinin conjugate

Poor delivery of insoluble anticancer drugs has so far precluded their clinical application. In this study, an efficient tumor targeted-nanoparticle delivery system, transferrin-eight-arm-polyethylene glycol–dihydroartemisinin nanoparticles (TF-8arm-PEG-DHA NPs) for the vehiculation of dihydroartemisinin (DHA) was first prepared and evaluated for its targeting efficiency and cytotoxicity in vitro and in vivo to Lewis lung carcinoma (LLC) cells, which overexpress transferrin receptors (TFRs). The synthesized TF-8arm-PEG–DHA NPs had high solubility (~102 fold of free DHA), relatively high drug loading (~10 wt% DHA), long circulating half-life and moderate particle size (~147 nm). The in vitro cytotoxicity and in vivo tumor growth inhibition studies in LLC-tumor bearing mice confirmed the enhanced efficacy of TF-modified 8arm-PEG-DHA NPs compared to free DHA and non-modified 8arm-PEG-DHA NPs. All these results together supported that the formulation developed in this work exhibited great potential as an effective tumor targeting delivery system for insoluble anticancer drugs.

Layer-by-Layer Fabrication of High-Performance Polyamide/ZIF-8 Nanocomposite Membrane for Nanofiltration Applications

The conventional blending fabrication for thin-film nanocomposite (TFN) membranes is to disperse porous fillers in aqueous/organic phases prior to interfacial polymerization, and the aggregation of fillers may lead to the significant decrease in membrane performance. To overcome this limitation, we proposed a novel layer-by-layer (LBL) fabrication to prepare a polyamide (PA)/ZIF-8 nanocomposite membrane with a multilayer structure: a porous substrate, a ZIF-8 interlayer, and a PA coating layer. The PA/ZIF-8 (LBL) membrane for nanofiltration applications was prepared by growing an interlayer of ZIF-8 nanoparticles on an ultrafiltration membrane through in situ growth and then coating it with an ultrathin PA layer through interfacial polymerization. The obtained PA/ZIF-8 (LBL) membrane exhibited both better permeance and selectivity than did the conventional PA/ZIF-8 TFN membrane because of the ZIF-8 in situ growth producing a ZIF-8 interlayer with more ZIF-8 nanoparticles but fewer aggregates. Compared with the pure PA membrane (the flux of 11.2 kg/m(2)/h and rejection of 99.6%) for dye removal, the obtained PA/ZIF-8 (LBL) membranes achieved a significant improvement in membrane permeance and selectivity. (Flux was up to 27.1 kg/m(2)/h, and the rejection reaches 99.8%.) This LBL fabrication is a promising methodology for other polymer nanocomposite membranes simultaneously having high permeance and good selectivity.

Nonequilibrium molecular dynamics simulation of water transport through carbon nanotube membranes at low pressurea)

Nonequilibrium molecular dynamics (NEMD) simulations are used to investigate pressure-driven water flow passing through carbon nanotube (CNT) membranes at low pressures (5.0 MPa) typical of real nanofiltration (NF) systems. The CNT membrane is modeled as a simplified NF membrane with smooth surfaces, and uniform straight pores of typical NF pore sizes. A NEMD simulation system is constructed to study the effects of the membrane structure (pores size and membrane thickness) on the pure water transport properties. All simulations are run under operating conditions (temperature and pressure difference) similar to a real NF processes. Simulation results are analyzed to obtain water flux, density, and velocity distributions along both the flow and radial directions. Results show that water flow through a CNT membrane under a pressure difference has the unique transport properties of very fast flow and a non-parabolic radial distribution of velocities which cannot be represented by the Hagen-Poiseuille or Navier-Stokes equations. Density distributions along radial and flow directions show that water molecules in the CNT form layers with an oscillatory density profile, and have a lower average density than in the bulk flow. The NEMD simulations provide direct access to dynamic aspects of water flow through a CNT membrane and give a view of the pressure-driven transport phenomena on a molecular scale.

Nonequilibrium molecular dynamics simulation of pressure-driven water transport through modified CNT membranes.

Nonequilibrium molecular dynamics (NEMD) simulations are presented to investigate the effect of water-membrane interactions on the transport properties of pressure-driven water flow passing through carbon nanotube (CNT) membranes. The CNT membrane is modified with different physical properties to alter the van der Waals interactions or the electrostatic interactions between water molecules and the CNT membranes. The unmodified and modified CNT membranes are models of simplified nanofiltration (NF) membranes at operating conditions consistent with real NF systems. All NEMD simulations are run with constant pressure difference (8.0 MPa) temperature (300 K), constant pore size (0.643 nm radius for CNT (12, 12)), and membrane thickness (6.0 nm). The water flow rate, density, and velocity (in flow direction) distributions are obtained by analyzing the NEMD simulation results to compare transport through the modified and unmodified CNT membranes. The pressure-driven water flow through CNT membranes is from 11 to 21 times faster than predicted by the Navier-Stokes equations. For water passing through the modified membrane with stronger van der Waals or electrostatic interactions, the fast flow is reduced giving lower flow rates and velocities. These investigations show the effect of water-CNT membrane interactions on water transport under NF operating conditions. This work can help provide and improve the understanding of how these membrane characteristics affect membrane performance for real NF processes.

The influence of dispersed phases on polyamide/ZIF-8 nanofiltration membranes for dye removal from water

To investigate the influence of different dispersed phases on polyamide (PA)/ZIF-8 membrane properties, three different fabrication methods for dispersing ZIF-8 nanoparticles were developed to prepare the PA/ZIF-8(A) membranes (in aqueous phases), PA/ZIF-8(O) membranes (in organic phases), and PA/ZIF-8(B) membrane (in both the aqueous and organic phases), respectively. These PA/ZIF-8 membranes were characterized in detail by XRD, DLS, XPS, FTIR, SEM, AFM, and contact angle measurements, the results showed that the structure properties of the PA/ZIF-8 membranes were significantly dependent on the dispersed phases and ZIF-8 concentrations. The nanofiltration performance of the PA/ZIF-8 membranes was investigated for application in removing dye (Congo red) from water. For the PA/ZIF-8(A) and PA/ZIF-8(O) membranes, the flux and rejection were both improved at 0.05–0.15% (w/v) ZIF-8 concentration in a single phase and the PA/ZIF-8(O) membranes exhibited slightly higher fluxes than the PA/ZIF-8(A) membranes due to the better dispersion of hydrophobic ZIF-8 in organic phases. The PA/ZIF-8(B) membrane prepared by 0.10% (w/v) ZIF-8 concentration in both the aqueous and organic phases showed the best membrane performance among all prepared PA/ZIF-8 membranes: the flux significantly increased to two times that of the pure PA membrane, and the rejection was nearly 100%. Compared with the PA/ZIF-8(A) and PA/ZIF-8(O) membranes, the improvement on membrane performance of the PA/ZIF-8(B) membrane was achieved by a combination of the high ZIF-8 loading, good ZIF-8 distribution, and fewer ZIF-8 aggregates in the PA/ZIF-8 selective layer.

Cellulose-graft-poly(L-lactic acid) nanoparticles for efficient delivery of anti-cancer drugs

Cellulose based carriers have the potential for sustained release of drugs, which can protect drugs and deliver them to the target site. Herein, BA-loaded cellulose-graft-poly(l-lactic acid) nanoparticles (CE-g-PLLA/BA NPs) were fabricated by employing cellulose (CE) and poly(l-lactic acid) (PLLA) as materials and betulinic acid (BA) as a model drug. Both drug-free and BA-loaded nanoparticles were spherical in shape with a uniform size of 100-170 nm. The release of BA from CE-g-PLLA/BA NPs was relatively slow. In vitro cytotoxicity studies with A549 and LLC cell lines suggested that CE-g-PLLA/BA NPs were slightly superior to BA in antitumor activity and CE-g-PLLA NPs were non-toxic. The antitumor effect of the CE-g-PLLA/BA NPs in a mouse tumor xenograft model exhibited much better tumor inhibition efficacy and fewer side effects than that of BA, strongly supporting their use as efficient carriers for anti-cancer therapy.

NiO-PTA supported on ZIF-8 as a highly effective catalyst for hydrocracking of Jatropha oil

Nickel oxide (NiO) and phosphotungstic acid (PTA) supported on a ZIF-8 (NiO-PTA/ZIF-8) catalyst was first synthesized and it showed high activity and good selectivity for the hydrocracking of Jatropha oil. The catalyst was characterized by SEM, SEM-EDS, TEM, N2 adsorption, FT-IR, XRD and XPS. Compared with the NiO-PTA/Al2O3 catalyst, the selectivity of C15-C18 hydrocarbon increased over 36%, and catalytic efficiency increased 10 times over the NiO-PTA/ZIF-8 catalyst. The prepared NiO-PTA/ZIF-8 catalyst was stable for a reaction time of 104 h and the kinetic behavior was also analyzed. This catalyst was found to bypass the presulfurization process, showing promise as an alternative to sulfided catalysts for green diesel production.

Novel Multiarm Polyethylene glycol-Dihydroartemisinin Conjugates Enhancing Therapeutic Efficacy in Non-Small-Cell Lung Cancer

The clinical application of dihydroartemisinin (DHA) has been hampered due to its poor water-solubility. To overcome this hurdle, we devised a novel polymer-drug conjugate, multiarm polyethylene glycol-dihydroartemisinin (PEG-DHA), made by linking DHA with multiarm polyethylene glycol. Herein, we investigated PEG-DHA on chemical structure, hydrolysis, solubility, hemolysis, cell cytotoxicity in vitro, and efficacy in vivo. The PEG-DHA conjugates have showed moderate drug loadings (2.82 ~ 8.14 wt%), significantly good water-solubilities (82- ~ 163-fold of DHA), excellent in vitro anticancer activities (at concentrations ≥8 μg/ml, showed only 15–20% cell viability) with potency similar to that of native DHA, and long blood circulation half-time (5.75- ~ 16.75-fold of DHA). Subsequent tumor xenograft assays demonstrated a superior therapeutic effect of PEG-DHA on inhibition of tumor growth compared with native DHA. The novel PEG-DHA conjugates can not only improve the solubility and efficacy of DHA but also show the potential of scale-up production and clinical application.

Water soluble multiarm-polyethylene glycol–betulinic acid prodrugs: design, synthesis, and in vivo effectiveness

Betulinic acid (BA) is a new type of cancer-fighting drug, but it is limited by its low water solubility and relatively short half-life in clinical applications. To overcome the shortcomings, BA prodrugs were prepared by using multiarm-polyethylene glycol linkers. The prodrugs exhibited high drug loading capacity (3.26–11.81 wt%), high water solubility (290–750 fold of free BA), and excellent in vitro anticancer activity. Subsequent tumor xenograft assays demonstrated the superior therapeutic effect of BA prodrugs on inhibition of tumor growth compared with free BA. Multiple intravenous injection of BA prodrugs equivalent to 10 mg of BA per kg resulted in the decrease of an established implanted murine Lewis lung carcinoma (percent tumor growth inhibition after treatment on day 20, 72.1–90.7%) in mice. These results strongly supported that the BA prodrugs are promising for cancer therapy.

Hydroprocessing of Jatropha Oil for Production of Green Diesel over Non-sulfided Ni-PTA/Al2O3 Catalyst

The non-sulfided Ni-PTA/Al2O3 catalyst was developed to produce green diesel from the hydroprocessing of Jatropha oil. The Ni-PTA/Al2O3 catalyst was prepared by one-pot synthesis of Ni/Al2O3 with the co-precipitation method and then impregnanting Ni/Al2O3 with PTA solution. The catalysts were characterized with BET, SEM-EDX, TEM, XRD, XPS, TGA and NH3-TPD. The Ni and W species of the Ni-PTA/Al2O3 catalyst were much more homogeneously distributed on the surface than that of commercial Al2O3. Catalytic performance in the hydroprocessing of Jatropha oil was evaluated by GC. The maximum conversion of Jatropha oil (98.5 wt%) and selectivity of the C15-C18 alkanes fraction (84.5 wt %) occurred at 360 °C, 3.0 MPa, 0.8 h−1. The non-sulfided Ni-PTA/Al2O3 catalyst is more environmentally friendly than the conventional sulfided hydroprocessing catalyst, and it exhibited the highest catalytic activity than the Ni-PTA catalyst supported with commercial Al2O3 grain and Al2O3 powder.