Effects of Control Factors on Protein-Polyelectrolyte Complex Coacervation.

Protein-polyelectrolyte complex coacervation is of particular interest for mimicking intracellular phase separation and organization. Yet, the challenge arises from regulating the coacervation due to the globular structure and anisotropic distributed charges of protein. Herein, we fully investigate the different control factors and reveal their effects on protein-polyelectrolyte coacervation. We prepared mixtures of BSA (bovine serum albumin) with different cationic polymers, which include linear and branched polyelectrolytes covering different spacer and charge groups, chain lengths, and polymer structures. With BSA-PDMAEMA [poly(N,N-dimethylaminomethyl methacrylate)] as the main investigated pair, we find that the moderate pH and ionic strength are essential for the adequate electrostatic interaction and formation of coacervate droplets. For most BSA-polymer mixtures, excess polyelectrolytes are required to achieve the full complexation, as evidenced by the deviated optimal charge mixing ratios from the charge stoichiometry. Polymers with longer chains or primary amine groups and a branched structure endow a strong electrostatic interaction with BSA and cause a bigger charge ratio deviation associated with the formation of solid-like coacervate complexes. Nevertheless, both the liquid- and solid-like coacervates hardly interrupt the BSA structure and activity, indicating the safe encapsulation of proteins by the coacervation with polyelectrolytes. Our study validates the crucial control of the diverse factors in regulating protein-polyelectrolyte coacervation, and the revealed principles shall be instructive for establishing other protein-based coacervations and boosting their potential applications.

Afterglow-Suppressed Lu2O3:Eu3+ Nanoscintillators for High-Resolution and Dynamic Digital Radiographic Imaging.

Lu2(1-x)Eu2xO3 nanoscintillators (x = 0.005, 0.01, 0.03, 0.05, 0.07, and 0.10) with red emission were synthesized by a coprecipitation method. It is found that their photo- and radioluminescence intensities increase with increasing Eu3+ concentration until x = 0.05. According to their concentration-dependent luminescence intensity ratios (I610(C2)/I582(S6)), the existing energy transfer from Eu3+(S6) (occupying S6 sites) to Eu3+(C2) (occupying C2 sites) can be confirmed. Based on the spectral data and density functional theory (DFT) calculations, the origin of Lu2O3:Eu3+ persistent luminescence at low concentration might be related to the tunneling processes between Eu3+ (occupying C2 and S6 sites) and oxygen interstitials (Oi×). After dispersing afterglow-suppressed Lu2O3:Eu3+ nanoscintillators into polymethyl methacrylate (PMMA) polymer-acetone solution, flexible PMMA-Lu2O3:Eu3+ composite films with high thermal stability and radiation resistance were fabricated by a doctor blade method. As the flexible composite film was used as an imaging plate, static X-ray images with high spatial resolution (5.5 lp/mm) under an extremely low dose of ∼1.1 µGyair can be acquired. When a watch with a moving second hand was used as an object, the dynamic X-ray imaging can be realized under a dose rate of 55 µGyair·s-1. Our results demonstrate that Lu2O3:Eu3+ nanoscintillators can be regarded as candidate materials for dynamic digital radiographic imaging.

Optical Gas-Cell Dynamic Adsorption in a Photoacoustic Spectroscopy-Based SOF2 and SO2F2 Gas Sensor.

SO2F2 and SOF2 are the main components from the decomposition of insulation gas SF6. Photoacoustic spectroscopy (PAS) has been acknowledged as an accurate sensing technique. Polar material adsorption for SO2F2 and SOF2 in the photoacoustic gas cell of PAS may affect detection efficiency. In this paper, the optical gas-cell dynamic adsorptions of four different materials and the detection effects on SO2F2 and SOF2 are theoretically analyzed and experimentally demonstrated. The materials, including grade 304 stainless steel (SUS304), grade 6061 aluminum alloy (Al6061), polyvinylidene difluoride (PVDC), and polytetrafluoroethylene (PTFE), were applied inside the optical gas cell. The results show that, compared with metallic SUS304 and Al6061, plastic PVDC and PTFE would reduce the gas adsorption of SO2F2 and SOF2 by 10 to 20% and shorten the response time during gas exchange. The complete gas defusing period in the experiment was about 30 s. The maximum variations of the 90% rising time between the different adsorption materials were approximately 3 s for SO2F2 and 6 s for SOF2, while the generated photoacoustic magnitudes were identical. This paper explored the material selection for PAS-based gas sensing in practical applications.

Primary angiomatoid fibrous histiocytoma of the mandible with EWSR1-ATF1 fusion in an adult patient: case report and review of literature.

OBJECTIVE: We report our diagnosis of a rare case of primary angiomatoid fibrous histiocytoma in the mandible of a 42-year-old male using next-generation sequencing to detect disease-specific EWSR1-ATF1 fusion. STUDY DESIGN: After the initial cone beam computerized tomography scan and reconstruction, we performed immunohistochemical staining and fluorescence in situ hybridization analysis on tissue samples to detect EWSR1 gene rearrangement. For the final diagnosis, we performed next-generation sequencing to detect disease-specific EWSR1-ATF1 fusion. RESULTS: FISH analysis showed approximately 55% of tumor cells with mostly isolated red signals, as well as several split red-green signals, indicating the presence of EWSR1 gene rearrangement. Next-generation sequencing analysis identified an EWSR1 exon9-ATF1 exon4 fusion, a diagnostic biomarker of angiomatoid fibrous histiocytoma (AFH). Based on the findings, we diagnosed primary AFH derived from the mandible. CONCLUSIONS: Next-generation sequencing is a powerful methodology for detecting disease-specific EWSR1-ATF1 fusion and diagnosing primary angiomatoid fibrous histiocytoma.

Green synthesis of phloroglucinol-urotropine porous polymer: Ingenious miniaturized solid phase extraction for efficient purification and determination of polycyclic aromatic hydrocarbons in lotus roots.

Polycyclic aromatic hydrocarbons (PAHs) posed a serious threat to food safety and human health due to long-term emission. In this work, a new method was established using phloroglucinol-urotropine porous polymer (PU-PP) in a pipette tip for solid phase extraction (PT-SPE) for the first time and used prior to determination of four PAHs (phenanthrene, anthracene, fluoranthene, and pyrene) in lotus roots. Synthesis of the PU-PP adsorbent was green compared with alternatives; urotropine was used as a cross-linker and ethanol-water as the solvent. PU-PP-based PT-SPE had the advantages of low solvent consumption, good purification, practicability, stability, and low-cost. The proposed pre-purification method offered low limits of detection (0.09-0.28 ng/g) and good recoveries (84.6-114.3 %, RSDs ≤ 5.6 %) for determination of the four PAHs, which were detected at trace concentrations in samples. This new method provides an alternative for monitoring trace pollutants in aquatic plant ingredients.

Flash nanoprecipitation with Gd(III)-based metallosurfactants to fabricate polylactic acid nanoparticles as highly efficient contrast agents for magnetic resonance imaging.

Polylactic acid (PLA) nanoparticles coated with Gd(III)-based metallosurfactants (MS) are prepared using a simple and rapid one-step method, flash nanoprecipitation (FNP), for magnetic resonance imaging (MRI) applications. By co-assembling the Gd(III)-based MS and an amphiphilic polymer, methoxy poly(ethylene glycol)-b-poly(ϵ-caprolactone) (mPEG-b-PCL), PLA cores were rapidly encapsulated to form biocompatible T1 contrast agents with tunable particle size and narrow size distribution. The hydrophobic property of Gd(III)-based MS were finely tuned to achieve their high loading efficiency. The size of the nanoparticles was easily controlled by tuning the stream velocity, Reynolds number and the amount of the amphiphilic block copolymer during the FNP process. Under the optimized condition, the relaxivity of the nanoparticles was achieved up to 35.39 mM-1 s-1 (at 1.5 T), which is over 8 times of clinically used MRI contrast agents, demonstrating the potential application for MR imaging.

Green protocol for the preparation of hydrophilic molecularly imprinted resin in water for the efficient selective extraction and determination of plant hormones from bean sprouts.

In this study, a novel and green synthesis of a new hydrophilic molecularly imprinted 3-aminophenol-hexamethylenetetramine (MIAPH) resin for the selective recognition and separation of plant hormones was developed. The MIAPH resin was obtained using 3-aminophenol as multifunctional monomer which introduced hydroxyl, amino, and imino groups simultaneously, and adenine was used as a dummy template for molecular imprinting. Meanwhile, hexamethylenetetramine released formaldehyde slowly through hydrolysis which was used as the cross-linking agent to avoid the direct and excessive use of toxic formaldehyde. The entire procedure was performed under mild conditions, and was facile, environmentally friendly and energy-efficient. The obtained MIAPH resin showed high specific recognition toward plant hormones and higher recoveries in bean sprouts compared to NIAPH, HLB, and C18. Various parameters affecting the extraction efficiency were optimized, and the calibration linearity of the MIAPH‒SPE‒HPLC method was determined from 0.07 to 2.86 mg kg-1 with a correlation coefficient (r) ≥ 0.9994 under the optimal conditions. Recoveries of spiked standards ranged from 90.2 to 99.1% for bean sprout with a relative standard deviation of ≤5.3%. Finally, the established MIAPH‒SPE‒HPLC method was successfully applied for the selective extraction and sensitive detection of plant hormones in a variety of complex vegetable matrices.

Attapulgite/hydrophilic molecularly imprinted monolithic resin composite for the selective recognition and sensitive determination of plant growth regulators in cucumbers.

In this study, through in-situ polymerization process, a novel composite of attapulgite/hydrophilic molecularly imprinted monolithic resin (AT/HMIMR) were prepared in pipette tips for extraction trace plant growth regulators in cucumbers. In the preparation procedure, fibrillar attapulgite nanoparticles were embedded to increase extraction capacity, polyethyleneglycol-6000 was employed as a dual-function porogen, that acted as both the structure-directing agent of the HMIMR and the attapulgite dispersant. N-(1-naphthyl) ethylenediamine dihydrochloride was used as a dummy template to accurate quantification on extraction procedures. Experimental parameters of AT/HMIMR for extracting plant growth regulators from cucumbers were optimized, and the results showed that the recoveries of ranged from 92.4% to 101.1% with relative standard deviations ≤ 6.5% (n = 3). Considering its microporous monolithic column structure, multiple adsorption mechanism, and specific selectivity, AT/HMIMR shows promise for applications that require specific recognition for the analytes in real complex samples.

Iridium complex nanoparticle mediated radiopharmaceutical-excited phosphorescence imaging.

We firstly perpared liposome coated [Ir(pq)2(bpy)]Cl (Ir@liposome) as a transducer for radiopharmaceutical (18F-FDG) excited phosphorescence imaging (REPI). Ir@liposome-based REPI exhibited deep tissue penetration and high signal-to-noise ratio in the tumor.

Preparation and Characterization of Size-Controlled Nanoparticles for High-Loading λ-Cyhalothrin Delivery through Flash Nanoprecipitation.

Environmental concerns and low efficacy pose a challenge for the application of traditional insecticide formulations. In this study, a series of λ-cyhalothrin (LC)-loaded nanoparticles (NPs) were produced by flash nanoprecipitation (FNP), and the parameters that influence nanoparticle size were systematically studied. The narrowly distributed and size-controllable NPs formed stable suspensions in aqueous solution without organic solvents. The amphiphilic block polymer PEG-PDLLA played an important role as a drug carrier, and the encapsulation content was as high as 99%. The obtained NPs with high loading of LC exhibited toxicity comparable to those of two commercial formulations at low doses. This confirms that FNP technology is a promising and scalable method for agrochemical delivery.

Fabrication of Charge-Conversion Nanoparticles for Cancer Imaging by Flash Nanoprecipitation.

Traditional charge-conversion nanoparticles (NPs) need the breakage of acid-labile groups on the surface, which impedes the rapid response to the acidic microenvironment. Here, we developed novel rodlike charge-conversion NPs with amphiphilic dextran- b-poly(lactic- co-glycolic acid), poly(2-(dimethylamino) ethylmethylacrylate)- b-poly(ε-caprolactone), and an aggregation-induced emission-active probe through flash nanoprecipitation (FNP). These NPs exhibit reversible negative-to-positive charge transition at a slightly acidic pH relying on the rapid protonation/deprotonation of polymers. The size and the critical charge-conversion pH can be further tuned by varying the flow rate and polymer ratio. Consequently, the charge conversion endows NPs with resistance to protein adsorption at physiological pH and enhanced internalization to cancer cells under acidic conditions. Ex vivo imaging on harvest organs shows that charge-conversion NPs were predominantly distributed in tumors after intravenous administration to mice due to the robust response of NPs to the acidic microenvironment in tumor tissue, whereas control NPs or free probes were broadly accumulated in tumor, liver, kidney, and lung. These results suggest the great potential of the current FNP strategy in the facile and generic fabrication of charge-conversion NPs for tumor-targeting delivery of drugs or fluorescent probes.

Morphology Tuning of Aggregation-Induced Emission Probes by Flash Nanoprecipitation: Shape and Size Effects on in Vivo Imaging.

Aggregation-induced emission (AIE) imaging probes have recently received considerable attention because of their unique property of high performance in the aggregated state and their imaging capability. However, the tendency of AIE molecules to aggregate into micron long irregular shapes, which significantly limits their application in vivo, is becoming a serious issue that needs to be addressed. Here, we introduce a novel engineering strategy to tune the morphology and size of AIE nanoaggregates, based on flash nanoprecipitation (FNP). Quinolinemalononitrile (ED) is encapsulated inside properly selected amphiphilic block copolymers of varying concentration. This leads to a variety of ED particle morphologies with different sizes. The shape and size are found to have strong influences on tumor targeting both in vitro and in vivo. The current results therefore indicate that the FNP method together with optimal choice of an amphiphilic copolymer is a universal method to systematically control the aggregation state of AIE materials and hence tune the morphology and size of AIE nanoaggregates, which is potentially useful for precise imaging at specific tumor sites.

Polydopamine-Functionalized Graphene Oxide Loaded with Gold Nanostars and Doxorubicin for Combined Photothermal and Chemotherapy of Metastatic Breast Cancer.

Breast cancer is the leading cancer type diagnosed in the female population, and cancer metastasis is the main reason for cancer-caused mortality. A novel nanoplatform is herein presented integrating polydopamine-functionalized nanosized reduced graphene oxide (NRGO), gold nanostars (GNS), and doxorubicin (DOX) (denoted as NRGO-GNS@DOX) for combinational treatment of metastatic breast cancer. Upon localized near infrared (NIR) laser irradiation, the NRGO-GNS@DOX nanocomposites induce significant cytotoxicity in 4T1 breast cancer cells due to a cumulative therapy effect of NRGO-GNS-elicited hyperthermia and DOX-induced cytotoxicity. Antitumor studies in orthotopic 4T1 breast tumor-bearing nude mice demonstrate that NRGO-GNS@DOX in combination with NIR laser irradiation inhibit the tumor growth and suppress the lung metastasis. Contribution of DOX-caused apoptosis of the cancer cells and hyperthermia-induced deconstruction of the tumor-associated blood vessels may account for the superior antitumor performance of the NRGO-GNS@DOX nanocomposites. These results imply a good potential of NRGO-GNS@DOX for combined photothermal and chemotherapy of the metastatic cancer.

Covalent functionalization of graphene oxide with biocompatible poly(ethylene glycol) for delivery of paclitaxel.

Graphene oxide (GO), a novel 2D nanomaterial prepared by the oxidation of natural graphite, has been paid much attention in the area of drug delivery due to good biocompatibility and low toxicity. In the present work, 6-armed poly(ethylene glycol) was covalently introduced into the surface of GO sheets via a facile amidation process under mild conditions, making the modified GO, GO-PEG (PEG: 65 wt %, size: 50-200 nm), stable and biocompatible in physiological solution. This nanosized GO-PEG was found to be nontoxic to human lung cancer A549 and human breast cancer MCF-7 cells via cell viability assay. Furthermore, paclitaxel (PTX), a widely used cancer chemotherapy drug, was conjugated onto GO-PEG via π-π stacking and hydrophobic interactions to afford a nanocomplex of GO-PEG/PTX with a relatively high loading capacity for PTX (11.2 wt %). This complex could quickly enter into A549 and MCF-7 cells evidenced by inverted fluorescence microscopy using Fluorescein isothiocyanate as a probe, and it also showed remarkably high cytotoxicity to A549 and MCF-7 cells in a broad range of concentration of PTX and time compared to free PTX. This kind of nanoscale drug delivery system on the basis of PEGylated GO may find potential application in biomedicine.

Tungsten oxide nanorods: an efficient nanoplatform for tumor CT imaging and photothermal therapy.

We report here a facile thermal decomposition approach to creating tungsten oxide nanorods (WO2.9 NRs) with a length of 13.1 ± 3.6 nm and a diameter of 4.4 ± 1.5 nm for tumor theranostic applications. The formed WO2.9 NRs were modified with methoxypoly(ethylene glycol) (PEG) carboxyl acid via ligand exchange to have good water dispersability and biocompatibility. With the high photothermal conversion efficiency irradiated by a 980 nm laser and the better X-ray attenuation property than clinically used computed tomography (CT) contrast agent Iohexol, the formed PEGylated WO2.9 NRs are able to inhibit the growth of the model cancer cells in vitro and the corresponding tumor model in vivo, and enable effective CT imaging of the tumor model in vivo. Our "killing two birds with one stone" strategy could be extended for fabricating other nanoplatforms for efficient tumor theranostic applications.