Nanoparticle delivery of chemotherapy combination regimen improves the therapeutic efficacy in mouse models of lung cancer.

The combination chemotherapy regimen of cisplatin (CP) and docetaxel (DTX) is effective against a variety of cancers. However, combination therapies present unique challenges that can complicate clinical application, such as increases in toxicity and imprecise exposure of tumors to specific drug ratios that can produce treatment resistance. Drug co-encapsulation within a single nanoparticle (NP) formulation can overcome these challenges and further improve combinations' therapeutic index. In this report, we employ a CP prodrug (CPP) strategy to formulate poly(lactic-co-glycolic acid)-poly(ethylene glycol) (PLGA-PEG) NPs carrying both CPP and DTX. The dually loaded NPs display differences in drug release kinetics and in vitro cytotoxicity based on the structure of the chosen CPP. Furthermore, NPs containing both drugs showed a significant improvement in treatment efficacy versus the free drug combination in vivo.

High performance isolation of circulating tumor cells by acoustofluidic chip coupled with ultrasonic concentrated energy transducer.

The isolation of circulating tumor cells (CTCs) from whole blood is a challenging task. Although various studies on the separation of CTCs by acoustofluidic devices have been reported, difficulties still persist, such as the complicated equipment, high cost, and difficult operation. Those problems should be resolved urgently. Herein, we developed an acoustofluidic chip separation system coupled with an ultrasonic concentrated energy transducer (UCET) system for efficient separation of CTCs. In the separation system, the acoustically sensitive particles were pre-focused by inertial forces of the PDMS chip channel structure. Then, the particles with different sizes were separated by acoustic radiation forces (ARF). In this study, the circulating tumor cells was simulated (CTCs-like particles) by aminated mesoporous acoustically sensitive particles (MSN@AM) encapsulated carboxylate polystyrene microspheres (PS-COOH). Subsequently, efficient CTCs-like particles separation was achieved by the acoustofluidic chip coupling system. This study effectively separated polystyrene microspheres carrying acoustically sensitive particles (MSN@AM@PS-COOH). However, the MSNs agglomerates and PS microspheres without acoustically sensitive particles did not show phenomenon of separation. This method allows to efficiently separate 2 µm MSNs agglomerates，8.0-8.9 µm PS microspheres and 10-10.5 µm MSN@AM@PS-COOH particles. It is demonstrated that the CTCs-like particles show more sensitive response, longer moving distance, and more obvious separation effect at the condition of the low frequency traveling wave sound field (20 kHz from UCET). This system can maintain the same separation with reduced amount of reagents used for cancer detection. It may provide a reliable basis for sorting out CTCs efficiently from the whole blood of cancer patients.

Effective defluoridation of water using nanosized UiO-66-NH2 encapsulated within macroreticular polystyrene anion exchanger.

Environmental concerns associated with the efficient defluoridation of contaminated water remain a substantial challenge. In this work, a new nanocomposite, UiO-66-NH2@PS+, was successfully fabricated via in situ precipitation of a water-stable metal-organic framework (UiO-66-NH2) inside a commercial polystyrene anion exchanger PS+. The as-formed nanocomposite UiO-66-NH2@PS+ was characterized using various morphological methods, which demonstrated that nanosized UiO-66-NH2 was homogenously dispersed within the inner pores of PS+. Batch adsorption experiments indicated that UiO-66-NH2@PS+ exhibited outstanding adsorption performance for fluoride over a broad pH range of 3.0-8.0. The saturated adsorption capacity of fluoride at 298 K was 27.5 and 32.8 mg/g for pH 6.5 and 4.5 with the adsorbent dosage of 0.5 g/L and initial concentration of 5-80 mg/L. Moreover, the utilization rate of active adsorption sites of UiO-66-NH2 was greatly improved after encapsulation. The XPS study indicated that the integrated effects of specific inner-sphere coordination and ligand exchange between fluoride and UiO-66-NH2 might be the dominant adsorption mechanism. Fixed-bed tests indicated that the UiO-66-NH2@PS+ column could successively produce clean water with bed volumes of 350 and 70 ([F-] <1.5 mg/L) from simulated fluoride-pollution water at pH 4.5 and 8.0, with a liquid velocity of 20 mL/h, and an empty bed contact time (EBCT) of 15 min, which was higher than that of the other materials. In addition, the exhausted UiO-66-NH2@PS+ was regenerated and reused for 5 times through complete regeneration, highlighting the potential feasibility of defluorination in practical applications.

Development and assessment of the efficacy and safety of human lung-targeting liposomal methylprednisolone crosslinked with nanobody.

Glucocorticoid (GC) hormone has been commonly used to treat systemic inflammation and immune disorders. However, the side effects associated with long-term use of high-dose GC hormone limit its clinical application seriously. GC hormone that can specifically target the lung might decrease the effective dosage and thus reduce GC-associated side effects. In this study, we successfully prepared human lung-targeting liposomal methylprednisolone crosslinked with nanobody (MPS-NSSLs-SPANb). Our findings indicate that MPS-NSSLs-SPANb may reduce the effective therapeutic dosage of MPS, achieve better efficacy, and reduce GC-associated side effects. In addition, MPS-NSSLs-SPANb showed higher efficacy and lower toxicity than conventional MPS.

Highly selective capture of phosphate ions from water by a water stable metal-organic framework modified with polyethyleneimine.

In this work, a series of polyethyleneimine (PEI) impregnated metal-organic framework (UiO-66) with varying PEI loadings were prepared and applied as sorbents to capture phosphate ions from water. As indicated by SEM and XRD analysis, PEI was dispersed on the outer surface and the inner pores of UiO-66. At 9.45% PEI loadings (UiO-66-3), the saturated adsorption capacity of phosphate reached 73.15 mg P/g at 298 K, which is superior to most sorbents ever reported. UiO-66-3 could sequestrate phosphate over a wide pH range from 2.0 to 7.0 with high efficiency. The sorption toward phosphate reached equilibrium in 50 min. Unlike commercial anion exchanger IRA-900, UiO-66-3 still exhibited high removal toward phosphate even large amount of coexisted anions were present. Successive sorption assay demonstrated that the removal efficiency of UiO-66-3 toward phosphate remained constant after six cyclic runs. All the above results indicated the great potential of UiO-66-3 as a promising sorbent for the decontamination of water from phosphate.

Development of a Hypoxic Radiosensitizer-Prodrug Liposome Delivery DNA Repair Inhibitor Dbait Combination with Radiotherapy for Glioma Therapy.

Gliomas are highly radioresistant tumors, mainly due to hypoxia in the core region of the gliomas and efficient DNA double-strand break repair. However, the design of a radiosensitizer incorporating the two above mechanisms is difficult and has rarely been reported. Thus, this study develops a hypoxic radiosensitizer-prodrug liposome (MLP) to deliver the DNA repair inhibitor Dbait (MLP/Dbait) to achieve the simultaneous entry of radiosensitizers with two different mechanisms into the glioma. MLP/Dbait effectively sensitizes glioma cells to X-ray radiotherapy (RT). Histological and microscopic examinations of dissected brain tissue confirm that MLP effectively delivers Dbait into the glioma. Furthermore, the combination of MLP/Dbait with RT significantly inhibits growth of the glioma, as assessed by in vivo bioluminescence imaging. These findings suggest that MLP is a promising candidate as a Dbait delivery system to enhance the effect of RT on glioma, owing to the synergistic effects of the two different radiosensitizers.

Surfactant protein-A nanobody-conjugated liposomes loaded with methylprednisolone increase lung-targeting specificity and therapeutic effect for acute lung injury.

The advent of nanomedicine requires novel delivery vehicles to actively target their site of action. Here, we demonstrate the development of lung-targeting drug-loaded liposomes and their efficacy, specificity and safety. Our study focuses on glucocorticoids methylprednisolone (MPS), a commonly used drug to treat lung injuries. The steroidal molecule was loaded into functionalized nano-sterically stabilized unilamellar liposomes (NSSLs). Targeting functionality was performed through conjugation of surfactant protein A (SPANb) nanobodies to form MPS-NSSLs-SPANb. MPS-NSSLs-SPANb exhibited good size distribution, morphology, and encapsulation efficiency. Animal experiments demonstrated the high specificity of MPS-NSSLs-SPANb to the lung. Treatment with MPS-NSSLs-SPANb reduced the levels of TNF-α, IL-8, and TGF-ß1 in rat bronchoalveolar lavage fluid and the expression of NK-κB in the lung tissues, thereby alleviating lung injuries and increasing rat survival. The nanobody functionalized nanoparticles demonstrate superior performance to treat lung injury when compared to that of antibody functionalized systems.

[A rare cause of pulmonary embolism]. / Seltene Ursache einer Lungenarterienembolie - Fall 8 / 2016.

HISTORY AND ADMISSION FINDINGS: We report on a patient with acute dyspnea after several vertebral body interventions, among others a kyphoplasty, that was performed a few days earlier. INVESTIGATIONS: In the computed tomography we prove a bilateral pulmonary embolism (cement and thrombus). There is no right heart failure. A deep vein thrombosis can be excluded by color-coded vascular ultrasound. DIAGNOSIS, TREATMENT AND COURSE: The pulmonary embolism is due to bone cement. The cement material is also found paravertebral, intraspinal and intraneuroforaminal. By conservative treatment using therapeutic anticoagulation and analgesic medication, the patient showed a rapid clinical improvement. CONCLUSIONS: In patients with cardiopulmonary symptoms after vertebroplasty and kyphoplasty, pulmonary embolism due to bone cement should be considered as a possible cause. The therapy depends on the extent of the cement embolism and the symptoms of the patient.

[Preparation of spider silk protein bilayer small diameter vascular scaffold and blood compatibility analysis in vitro].

OBJECTIVE: To prepare a spider silk protein bilayer small diameter vascular scaffold using electrospinning, and to observe the blood compatibility in vitro. METHODS: The Arg-Gly-Asp-recombinant spider silk protein (pNSR16), polycaprolactone (PCL), gelatin (Gt), and heparin (Hep) were blended. Spider silk protein bilayer small diameter vascular scaffold (experimental group) was prepared by electrospinning, with pNSR16 : PCL : Hep (5 : 85 : 10, W/W) hybrid electrospun solution as inner spinning solution and pNSR16 : PCL : Gt (5 : 85 : 10, W/W) hybrid electrospun solution as outer spinning solution, but pNSR16 : PCL (5 : 85, W/W) hybrid electrospun solution was used as inner spinning solution in control group. The scaffold structure of experimental group was observed under scanning electron microscope (SEM); and the hemolysis rate, recalcification clotting time, dynamic clotting time, platelet adhesion, and platelet activation in vitro were compared between 2 groups. RESULTS: SEM results showed that bilayer fibers of scaffold were quite different in experimental group; the diameter distribution of inner layer fibers was relatively uniform with small pores, however diameter difference of the outer layer fiber was relatively big with big pores. The contact angle, hemolysis rate, recalcification clotting time, and P-selectin expression of scaffold were (35 +/- 3) degrees, 1.2% +/- 0.1%, (340 +/- 11) s, and 0.412 +/- 0.027 respectively in experimental group, and were (70 +/- 4) degrees, 1.9% +/- 0.1%, (260 +/- 16) s, and 0.678 +/- 0.031 respectively in control group; significant difference were found in indexes between 2 groups (P < 0.05). With the extension of time, the curve of coagulation time in experimental group sloped downward slowly and had a long time; the blood clotting index values before 30 minutes were significantly higher than those in control group (P < 0.05). Platelet adhesion test showed that the scaffold surface almost had no platelet adhesion in experimental group. CONCLUSION: The spider silk protein bilayer small diameter vascular scaffold could be prepared through electrospinning, and it has good blood compatibility in vitro.

Effect of sulfate on Cu(II) sorption to polymer-supported nano-iron oxides: behavior and XPS study.

Iron oxides tend to be immobilized within nanoporous supports to improve their feasibility for practical environmental remediation including arsenic and heavy metal removal. Contrary to the co-ions, little is known concerning the effect of counter ions on the performance of the resultant composites. In this study, two hybrid sorbents (denoted as HFO-PS(-) and HFO-PS(0), respectively) were prepared by loading hydrous ferric oxide (HFO) nanoparticles onto two polystyrene beads: PS(-), negatively charged with sulfonic acid groups, and PS(0), covalently bonded with neutral chloromethyl groups. Effects of sulfate on their sorption toward Cu ions were investigated. Consistent with the case in bulky HFO particles, the amount of Cu adsorbed on HFO-PS(0) was markedly promoted by introducing sulfate. As for HFO-PS(-), with monovalent cation as background (Na(+)), it exhibited an apparent decrease in Cu sorption as a result of the competing effect of Na ions and the Cu-SO(4) complexation in solution. Contrarily, the adsorbed Cu was increased by introducing sulfate in the divalent cation background (Ca), because sulfate ions were allowed to access to the loaded HFO nanoparticles due to the screening of the sulfonic acid groups caused by Ca ions. XPS spectroscopy further demonstrated that besides the electrostatic effects, the formation of Cu-SO(4) ternary complexes also accounted for the enhanced Cu sorption on both bulky HFO and hybrid HFO sorbents in the presence of sulfate. These results indicated that the effect of counter-ion ligands on metal adsorption to hybrid iron oxides was largely dependent on the surface properties of the host materials.

Improved blood compatibility of Mg-1.0Zn-1.0Ca alloy by micro-arc oxidation.

Magnesium and its alloys have been used in the recent development of lightweight, biodegradeable implant materials. However, the corrosion properties of magnesium limit its usefulness. In a previous study, a micro-arc oxidation (MAO) method was used to modify a Mg-1.0 wt % Zn-1.0 wt % Ca alloy surface, with the purpose of improving the corrosion resistance of Mg alloys. However, the blood compatibility of MAO-treated Mg alloy is unknown. Results of cytotoxicity assays with bone marrow-derived mesenchymal stem cells showed that extracts of MAO-treated alloy significantly decreased cytotoxicity compared to titanium alloy extract. Results of blood compatibility tests showed that the MAO group had a decreased hemolytic ratio (2.25%) compared to the untreated Mg alloy group (24.58%) (p < 0.001). The MAO group showed significantly shorter prothrombin and thrombin times and significantly longer activated partial thromboplastin time than the untreated Mg alloy group. Arachidonic acid- and adenosine diphosphate-induced platelet aggregations were significantly decreased by the untreated Mg alloy extract, and they were less affected by extract of MAO-treated Mg alloy. In conclusion, MAO-treated Mg-1.0 wt % Zn-1.0 wt % Ca alloy exhibits favorable blood compatibility characteristics and may be useful in the development of magnesium implant materials.

Highly efficient removal of heavy metals by polymer-supported nanosized hydrated Fe(III) oxides: behavior and XPS study.

The present study developed a polymer-based hybrid sorbent (HFO-001) for highly efficient removal of heavy metals [e.g., Pb(II), Cd(II), and Cu(II)] by irreversibly impregnating hydrated Fe(III) oxide (HFO) nanoparticles within a cation-exchange resin D-001 (R-SO(3)Na), and revealed the underlying mechanism based on X-ray photoelectron spectroscopy (XPS) study. HFO-001 combines the excellent handling, flow characteristics, and attrition resistance of conventional cation-exchange resins with the specific affinity of HFOs toward heavy metal cations. As compared to D-001, sorption selectivity of HFO-001 toward Pb(II), Cu(II), and Cd(II) was greatly improved from the Ca(II) competition at greater concentration. Column sorption results indicated that the working capacity of HFO-001 was about 4-6 times more than D-001 with respect to removal of three heavy metals from simulated electroplating water (pH approximately 4.0). Also, HFO-001 is particularly effective in removing trace Pb(II) and Cd(II) from simulated natural waters to meet the drinking water standard, with treatment volume orders of magnitude higher than D-001. The superior performance of HFO-001 was attributed to the Donnan membrane effect exerted by the host D-001 as well as to the impregnated HFO nanoparticles of specific interaction toward heavy metal cations, as further confirmed by XPS study on lead sorption. More attractively, the exhausted HFO-001 beads can be effectively regenerated by HCl-NaCl solution (pH 3) for repeated use without any significant capacity loss.

Efficient removal of aromatic sulfonates from wastewater by a recyclable polymer: 2-naphthalene sulfonate as a representative pollutant.

As a family of hydrophobic ionizable organic compounds, aromatic sulfonates can be present at high levels in industrial wastewaters. They tend to exist as anions over a wide range of pH and cannot be effectively trapped by conventional adsorbents. In the current study, a recyclable acrylic ester polymer (NDA-801) was synthesized for effective removal of aromatic sulfonates from wastewater of high acidity (e.g., pH < 1) and inorganic salts (e.g., approximately 5-10% Na2SO4 in mass), for which sodium 2-naphthalene sulfonate (2-NS) was chosen as a representative target contaminant 2-NS uptake onto NDA-801 increased with the increasing acidity of the solution. The zeta potential of NDA-801 measured at different pH levels as well as batch 2-NS adsorption from methanol/water binary systems demonstrated the favorable roles of electrostatic and hydrophobic interaction in 2-NS adsorption. As compared to a granular activated carbon GAC-1, NDA-801 exhibited much higher removal efficiency and capacity of 2-NS in fixed-bed adsorption. Moreover, the exhausted NDA-801 beads by 2-NS can be completely regenerated by water wash for repeated use, which is more economically desirable than by other regenerants, such as NaOH solution. Continuous column adsorption-regeneration cycles indicated negligible capacity loss of NDA-801 during operation and further validated its feasibility for potential application in associated wastewater treatment.