Understanding Quasi-Static and Dynamic Characteristics of Organic Ferroelectric Field Effect Transistors.

Leveraging poly(vinylidene fluoride-trifluoroethylene) [(PVDF-TrFE)] as the dielectric, we fabricated organic ferroelectric field-effect transistors (OFe-FETs). These devices demonstrate quasi-static transfer characteristics that include a hysteresis window alongside transient phenomena that bear resemblance to synaptic plasticity-encapsulating excitatory postsynaptic current (EPSC) as well as both short-term and long-term potentiation (STP/LTP). We also explore and elucidate other aspects such as the subthreshold swing and the hysteresis window under dynamic state by varying the pace of voltage sweeps. In addition, we developed an analytical model that describes the electrical properties of OFe-FETs, which melds an empirical formula for ferroelectric polarization with a compact model. This model agrees well with the experimental data concerning quasi-static transfer characteristics, potentially serving as a quantitative tool to improve the understanding and design of OFe-FETs.

Magnetic solid phase extraction followed by in-situ derivatization with core-shell structured titanium dioxide coated ferriferrous oxide microspheres for determination of alendronate in plasma.

In this study, for the first time, magnetic solid phase extraction (MSPE) was combined with in-situ derivatization to determine alendronate in plasma. TiO2 coated Fe3O4 microspheres (denoted as Fe3O4@TiO2) were synthesized via polydopamine coating, titanium ions immobilizing and calcination steps. The as-prepared microspheres could selectively extract alendronate and be quickly isolated from plasma. The drug-adsorbed Fe3O4@TiO2 microspheres were then directly incubated in derivatization reagent solution to perform novel in-situ derivatization and elution procedure, in which the derivatized alendronate lost its affinity to TiO2 and was spontaneously eluted for further LC-MS/MS detection. Satisfactory results were obtained on the creative attempt to couple dispersive magnetic solid phase extraction with in-situ derivatization. The developed method was validated and demonstrated good linearity (0.05-500 ng mL-1), low detection limit (20 pg mL-1), great accuracy (100.6% to 105.3%) and precision (RSDs<5.27%). Manual operation and analysis time could be greatly reduced compared to other reported methods. The method was successfully applied to a pharmacokinetic study in beagle dogs.

A composite consisting of sulfo-functionalized magnetic graphene and mesoporous silica for extraction of metformin and glimepiride prior to their determination by liquid chromatography tandem mass spectrometry.

A new sorbent was synthesized for restricted-access matrix solid phase extraction (RAM-SPE) of the diabetes drugs metformin (MET) and glimepiride (Glim). Mesoporous silica layers were placed on Fe3O4-magnetized graphene modified with sulfo-functionalized pore walls (denoted as magG@mSiO2-SO3H composites). The composites have a large specific surface (173 m2·g-1), appropriate pore sizes (typically 3.7 nm), and sulfo-functionalized pore walls. Magnetic separation can be accomplished within 10 s. The unique properties of the composites allow both MET and Glim to be selectively and quickly extracted from plasma sample. Following magnetic separation and elution by 50% aqueous acetonitrile with 4% ammonium solution, the two drugs were quantified by LC-MS/MS analysis. The assay has high selectivity, good linearity (2.5-4000 ng•mL-1 for MET and 0.02-1600 ng•mL-1 for Glim), a low detection limit (as low as 60 pg•mL-1 for MET and 1 pg•mL-1 for Glim), excellent recovery (above 92.2%), and good precision (RSDs <12%). The method was successfully applied in a pharmacokinetic study in beagle dogs. Graphical abstract Schematic representation of the synthesis of sulfo-functionalized magnetic graphene/mesoporous silica composites, giving a material of type magG@mSiO2-SO3H. Results showed its great potential as a feasible and alternative adsorbent for the selective extraction of MET and Glim from complicated biological samples.

In Situ Atmospheric Deposition of Ultrasmooth Nickel Oxide for Efficient Perovskite Solar Cells.

Organic-inorganic perovskite solar cells have attracted significant attention due to their remarkable performance. The use of alternative metal-oxide charge-transport layers is a strategy to improving device reliability for large-scale fabrication and long-term applications. Here, we report solution-processed perovskite solar cells employing nickel oxide hole-extraction layers produced in situ using an atmospheric pressure spatial atomic-layer deposition system, which is compatible with high-throughput processing of electronic devices from solution. Our sub-nanometer smooth (average roughness of ≤0.6 nm) oxide films enable the efficient collection of holes and the formation of perovskite absorbers with high electronic quality. Initial solar-cell experiments show a power-conversion efficiency of 17.1%, near-unity ideality factors, and a fill factor of >80% with negligible hysteresis. Transient measurements reveal that a key contributor to this performance is the reduced luminescence quenching trap density in the perovskite/nickel oxide structure.

Magnetic microspheres modified with Ti(IV) and Nb(V) for enrichment of phosphopeptides.

Magnetic microspheres (Fe3O4) were coated with polydopamine (PDA) and loaded with the metal ions Ti(IV) and Nb(V) to give a material of type Fe3O4@PDA-Ti/Nb. It is shown to be useful for affinity chromatography and for enrichment of phosphopeptides from both standard protein solutions and real samples. For comparison, such microspheres loaded with single metal ions only (Fe3O4@PDA-Ti and Fe3O4@PDA-Nb) and their physical mixtures were also investigated under identical conditions. The binary metal ion-loaded magnetic microspheres display better enrichment efficiency than the single metal ion-loaded microspheres and their physical mixture. Both multiphosphopeptides and monophosphopeptides can be extracted. The Fe3O4@PDA-Ti/Nb microspheres exhibit ultra-high sensitivity (the lowest detection amount being 2 fmol) and selectivity at a low mass ratio such as in case of ß-casein/BSA (1:1000). Graphical abstract Magnetic microspheres (Fe3O4) were coated with polydopamine (PDA) and loaded with the metal ions Ti(IV) and Nb(V) to give a material of type Fe3O4@PDA-Ti/Nb. Results showed its great potential as an affinity probe in phosphoproteome research due to rapid magnetic separation of phosphopeptides, ultrahigh sensitivity and selectivity, and remarkable reusability.

Synthesis of magnetic graphene/mesoporous silica composites with boronic acid-functionalized pore-walls for selective and efficient residue analysis of aminoglycosides in milk.

In this study, magnetic graphene/mesoporous silica composites with boronic acid-functionalized pore-walls were synthesized for the first time by a two-step post-graft method. The obtained nano-composites were proven to hold many attractive features such as large specific surface area, uniform mesopores, high magnetic responsibility, and boronic acid-functionalized inner pore-walls. Aminoglycoside residues in milk were extracted using MG@mSiO2-APB composites as restricted access matrix dispersive solid phase extraction adsorbents through the interaction between boronic acid groups and glucoside structures. Extraction conditions were optimized by studying the SPE parameters. Limits of detection of the method were as low as 5ngmL-1 for streptomycin) and 2ngmL-1 for dihydrostreptomycin. Finally, magnetic graphene/mesoporous silica composites with boronic acid-functionalized pore-walls were successfully applied to residue analysis in milk samples. Compared to the traditional extraction methods, using this nano-composites for aminoglycoside residues analysis in milk is more sensitive, effective and convenient.

A Vertical Organic Transistor Architecture for Fast Nonvolatile Memory.

A new device architecture for fast organic transistor memory is developed, based on a vertical organic transistor configuration incorporating high-performance ambipolar conjugated polymers and unipolar small molecules as the transport layers, to achieve reliable and fast programming and erasing of the threshold voltage shift in less than 200 ns.

Cyclopamine disrupts tumor extracellular matrix and improves the distribution and efficacy of nanotherapeutics in pancreatic cancer.

The dense extracellular matrix in pancreatic ductal adenocarcinoma dramatically reduces the penetration and efficacy of nanotherapeutics. Disruption of the tumor extracellular matrix may help improve the distribution and efficacy of nanotherapeutics in pancreatic cancer. In this study, we tested whether cyclopamine, a special inhibitor of the hedgehog signaling pathway with powerful anti-fibrotic activity, could promote the penetration and efficacy of nanotherapeutics in pancreatic cancer. It was shown that cyclopamine disrupted tumor extracellular fibronectins, decompressed tumor blood vessels, and improved tumor perfusion. Furthermore, cyclopamine improved the accumulation and intratumoral distribution of i.v.-administered fluorescence indicator-labeled nanoparticles. Finally, cyclopamine also significantly improved the tumor growth inhibition effect of i.v.-injected nanotherapeutics in pancreatic tumor xenograft mouse models. Thus, cyclopamine may have great potential to improve the therapeutic effects of nanomedicine in patients with pancreatic cancer.

Fibrin degradation by rtPA enhances the delivery of nanotherapeutics to A549 tumors in nude mice.

Effective drug delivery to a tumor depends on favorable blood perfusion within the tumor. As an important component of tumor extracellular matrix, fibrin is abundant near tumor vessels. Inspired by the distinct distribution pattern and vessel-dependent production of fibrin, we hypothesized that fibrin depletion in tumors decompresses tumor vessels to improve tumor blood perfusion and accordingly enhance drug delivery to tumors rich in vessels. In the present study, we attempted to employ a clinically used thrombolytic drug, recombinant tissue plasminogen activator (rtPA), to modulate fibrin deposition in tumors. We then combined this drug with a nanoparticle drug delivery system for tumor therapy. RtPA treatment (25 mg/kg/d i. p. administration for two weeks) successfully depleted fibrin deposition and enhanced blood perfusion within A549 tumor xenografts. Furthermore, rtPA treatment also improved the in vivo delivery of 115-nm nanoparticles to tumor tissues. Finally, rtPA combined with therapeutic agent-loaded nanoparticles resulted in the most effective shrinkage of A549 tumor xenografts compared with the control groups. Overall, the present study provides a new strategy to enhance the delivery of nanotherapeutics to tumors rich in vessels.

Enhanced Antitumor Activity of EGFP-EGF1-Conjugated Nanoparticles by a Multitargeting Strategy.

Tumor stromal cells have been increasingly recognized to interact with tumor parenchyma cells and promote tumor growth. Therefore, we speculated that therapeutics delivery to both parenchyma cells and stromal cells simultaneously might treat a tumor more effectively. Tissue factor (TF) was shown to be extensively located in a tumor and was abundantly sited in both tumor parenchyma cells and stromal cells including neo-vascular cells, tumor-associated fibroblasts, and tumor-associated macrophages, indicating it might function as a favorable target for drug delivery to multiple cell types simultaneously. EGFP-EGF1 is a fusion protein derived from factor VII, the natural ligand of TF. It retains the specific TF binding capability but does not cause coagulation. In the present study, a nanoparticle modified with EGFP-EGF1 (ENP) was constructed as a multitargeting drug delivery system. The protein binding experiment showed EGFP-EGF1 could bind well to A549 tumor cells and other stromal cells including neo-vascular cells, tumor-associated fibroblasts, and tumor-associated macrophages. Compared with unmodified nanoparticles (NP), ENP uptake by A549 cells and those stromal cells was significantly enhanced but inhibited by excessive free EGFP-EGF1. In addition, ENP induced more A549 tumor cell apoptosis than Taxol and NP when paclitaxel (PTX) was loaded. In vivo, ENP accumulated more specially in TF-overexpressed A549 tumors by in vivo imaging, mainly regions unoccupied by factor VII and targeted tumor parenchyma cells as well as different types of stromal cells by immunofluorescence staining. Treatment with PTX-loaded ENP (ENP-PTX) significantly reduced the A549 tumor growth in nude mice while NP-PTX- and Taxol-treated mice had lower response to the therapy. Furthermore, H&E and TUNEL staining revealed that ENP-PTX induced more severe tumor necrosis and more extensive cell apoptosis. Altogether, the present study demonstrated that ENP could target multiple key cell types in tumors through TF, which could be utilized to improve the therapeutic effect of anticancer drugs.

Fibrin-targeting peptide CREKA-conjugated multi-walled carbon nanotubes for self-amplified photothermal therapy of tumor.

Inability of nanomedicine to efficiently home to tumor site still poses great challenge in tumor drug delivery. Inspired by the amplified formation of fibrin in clotting cascade, a self-amplified drug delivery system was developed for tumor photothermal therapy (CMWNTs-PEG) using multi-walled carbon nanotubes (MWNTs) with favorable photothermal effect as the vector, polyethylene glycol as the shelter, CREKA peptide with special affinity for fibrin as the targeting moiety and NIR illumination as the external power. The self-amplified targeting property was carefully characterized. The in vivo temperature monitoring experiment demonstrated that CMWNTs-PEG could significantly elevate the temperature in the tumor region than its counterpart 24 h post an initial NIR illumination. The in vivo imaging and biodistribution experiment showed IR783-labeled CMWNTs-PEG with illumination could accumulate in tumors tissues about 6.4-fold higher than control group, much stronger than other treatment groups. In vivo distribution experiments revealed Cy3-labeled CMWNTs-PEG could deposit on the wall of tumor vessels, intravascular and extravascular spaces, far more extensive than its counterpart in tumor slices. The pharmacodynamics experiment revealed that after four times of illumination, the CMWNTs-PEG almost totally eradiated the tumor xenografts. Altogether, the self-amplified targeting system CMWNTs-PEG showed strong tumor targeting capacity and powerful photothermal therapeutic efficacy.

UPA-sensitive ACPP-conjugated nanoparticles for multi-targeting therapy of brain glioma.

Now it is well evidenced that tumor growth is a comprehensive result of multiple pathways, and glioma parenchyma cells and stroma cells are closely associated and mutually compensatory. Therefore, drug delivery strategies targeting both of them simultaneously might obtain more promising therapeutic benefits. In the present study, we developed a multi-targeting drug delivery system modified with uPA-activated cell-penetrating peptide (ACPP) for the treatment of brain glioma (ANP). In vitro experiments demonstrated nanoparticles (NP) decorated with cell-penetrating peptide (CPP) or ACPP could significantly improve nanoparticles uptake by C6 glioma cells and nanoparticles penetration into glioma spheroids as compared with traditional NP and thus enhanced the therapeutic effects of its payload when paclitaxel (PTX) was loaded. In vivo imaging experiment revealed that ANP accumulated more specifically in brain glioma site than NP decorated with or without CPP. Brain slides further showed that ACPP contributed to more nanoparticles accumulation in glioma site, and ANP could co-localize not only with glioma parenchyma cells, but also with stroma cells including neo-vascular cells and tumor associated macrophages. The pharmacodynamics results demonstrated ACPP could significantly improve the therapeutic benefits of nanoparticles by significantly prolonging the survival time of glioma bearing mice. In conclusion, the results suggested that nanoparticles modified with uPA-sensitive ACPP could reach multiple types of cells in glioma tissues and provide a novel strategy for glioma targeted therapy.