Hyperbranched Polymer Induced Antibacterial Tree-Like Nanofibrous Membrane for High Effective Air Filtration.

The air filtration materials with high efficiency, low resistance, and extra antibacterial property are crucial for personal health protection. Herein, a tree-like polyvinylidene fluoride (PVDF) nanofibrous membrane with hierarchical structure (trunk fiber of 447 nm, branched fiber of 24.7 nm) and high filtration capacity is demonstrated. Specifically, 2-hydroxypropyl trimethyl ammonium chloride terminated hyperbranched polymer (HBP-HTC) with near-spherical three-dimensional molecular structure and adjustable terminal positive groups is synthesized as an additive for PVDF electrospinning to enhance the jet splitting and promote the formation of branched ultrafine nanofibers, achieving a coverage rate of branched nanofibers over 90% that is superior than small molecular quaternary ammonium salts. The branched nanofibers network enhances mechanical properties and filtration efficiency (99.995% for 0.26 µm sodium chloride particles) of the PVDF/HBP-HTC membrane, which demonstrates reduced pressure drop (122.4 Pa) and a quality factor up to 0.083 Pa-1 on a 40 µm-thick sample. More importantly, the numerous quaternary ammonium salt groups of HBP-HTC deliver excellent antibacterial properties to the PVDF membranes. Bacterial inhibitive rate of 99.9% against both S. aureus and E. coli is demonstrated in a membrane with 3.0 wt% HBP-HTC. This work provides a new strategy for development of high-efficiency and antibacterial protection products.

In Vivo Real-Time Imaging of Extracellular Vesicles in Liver Regeneration via Aggregation-Induced Emission Luminogens.

Extracellular vesicles (EVs) attract much attention in liver pathology because they regulate cell-cell communication and many pathophysiological events by transferring their cargos. Monitoring and understanding the in vivo fate and therapeutic capacity of these EVs is critical for the development and optimization of EV-based diagnosis and therapy. Herein, we demonstrate the use of an aggregation-induced emission luminogen, DPA-SCP, for the real-time tracking of EVs derived from human placenta-derived mesenchymal stem cells (MSCs) and their therapeutic effects in a mouse acute liver injury (ALI) model. In vitro, DPA-SCP does not alter the inherent characteristics of MSC-derived EVs and shows extremely low toxicity. Moreover, DPA-SCP exhibited superior labeling efficiency and tracking capability to the most popular commercial EV trackers, PKH26 and DiI. In vivo, DPA-SCP precisely and quantitatively tracked the behaviors of EVs for 7 days in the mouse ALI model without influencing their regenerative capacity and therapeutic efficacy. The therapeutic effects of EVs may attribute to their ability for reducing inflammatory cell infiltration, enhancing cell survival and antiapoptotic effects. In conclusion, DPA-SCP with an AIE signature serves as a favorable and safe tracker for in vivo real-time imaging of EVs in liver regeneration.

Nano-biotinylated liposome-based immunoassay for the ultrasensitive detection of protein biomarker in urine.

With the development of proteomics and the continuous discovery of biomarkers of trace proteins, it is important to accurately quantify low abundance protein, especially in urine for clinical diagnostics. In this paper, we reported a novel nano-biotinylated liposome-based immuno-loop-mediated isothermal amplification (LI-LAMP) for the ultrasensitive detection of REG1A (a biomarker for pancreatic ductal adenocarcinoma (PDAC) in urine) with high specificity. The detection range was 1µg/mL to 1fg/mL, with a detection limit of 1fg/mL, and no cross-reactivity was observed to occur in this assay. Compared with the amount of REG1A added, REG1A recovery using this method was 130% and 89%. Detection of REG1A concentrations using the LI-LAMP assay from real samples were in good agreement with those determined using ELISA, and relative deviations were not more than 10%. LI-LAMP shows good potential as a clinical diagnostic assay.

Magnetic-bioluminescent-nanoliposomes for ultrasensitive and portable detection of protein biomarkers in blood.

Protein biomarkers play an important role in the diagnosis and treatment of disease. Herein, we report an ultrasensitive magnetic-bioluminescent-nanoliposome based technique using a portable ATP luminometer for the point-of-care testing (POCT) of protein biomarkers in blood. In this study, we use alpha-fetoprotein (AFP, a protein biomarker associated with hepatocellular carcinoma) as a model protein. The bioluminescent nanoliposomes conjugated to magnetic particles (LBM) enabled target protein capture, isolation and detection. In this assay, we use a portable magnetic bead separation pen to simplify the steps. The output RLUs (relative light units) had a linear correlation with AFP concentration between 0.05 and 1000 ng/mL, with a limit of detection of 0.016 ng/mL. Our LBM assay for AFP based on the portable luminometer exhibited high specificity for AFP, with no cross-reactivity with other proteins tested at 25 ng/mL. Forty clinical samples (twenty AFP positive and twenty AFP negative) were tested by the LBM assay, and the results were in good agreement with those determined by electrochemiluminescence, with relative deviations of less than 10%. The successful application of magnetic-bioluminescent-nanoliposomes with a portable ATP luminometer system to detect protein biomarkers in blood has opened a new avenue for biomarker testing. Thus, our LBM assay holds great potential as a POCT assay for use in clinical diagnostics.

Magnetic-Immuno-Loop-Mediated Isothermal Amplification Based on DNA Encapsulating Liposome for the Ultrasensitive Detection of P-glycoprotein.

Determination of proteins, especially low-abundance proteins with high sensitivity and specificity, is essential for characterizing proteomes and studying their biochemical functions. Herein, a novel Magnetic-Immuno-Loop-Mediated Isothermal Amplification (Im-LAMP) based on DNA-encapsulating liposomes (liposome-Im- LAMP), was developed for trace amounts of proteins. To the best of our knowledge, this is our first report about the magnetic Im-LAMP approach based on liposomes encapsulated template DNA as the detection reagent. The DNA template was released from liposomes and then initiated an Im-LAMP reaction, generating the fluorescence signal with high sensitivity and rapidity. This technique was applied for the determination of P-glycoprotein as a model protein. It was demonstrated that the technique exhibited a dynamic response to P-glycoprotein ranging from 1.6*10-2 to 160 pg/ml with a greatly low detection limit of 5*10-3 pg/ml (5 fg/ml) which is substantially better than conventional enzyme-linked immunosorbent assays (ELISA). This ultra sensitivity was attributed to the LAMP reaction initiated by the enormous DNA targets encapsulated in liposomes. This magnetic liposome-Im-LAMP as an alternative approach is attractive for applications in other low-abundance proteins detection in clinical diagnostics.

ZnO-Based Nanoplatforms for Labeling and Treatment of Mouse Tumors without Detectable Toxic Side Effects.

ZnO quantum dots (QDs) were synthesized with polymer shells, coordinated with Gd(3+) ions and adsorbed doxorubicin (DOX) together to form a new kind of multifunctional ZnO-Gd-DOX nanoplatform. Such pH sensitive nanoplatforms were shown to release DOX to cancer cells in vitro and to mouse tumors in vivo, and reveal better specificity and lower toxicity than free DOX, and even better therapeutic efficacy than an FDA approved commercial DOX-loading drug DOX-Liposome Injection (DOXIL, NDA#050718). The ZnO-Gd-DOX nanoplatforms exhibited strong red fluorescence, which benefited the fluorescent imaging on live mice. Due to the special structure of ZnO-Gd-DOX nanoparticles, such nanoplatforms possessed a high longitudinal relaxivity r1 of 52.5 mM(-1) s(-1) at 0.55 T, which was superior to many other Gd(3+) based nanoparticles. Thus, both fluorescence labeling and magnetic resonance imaging could be applied simultaneously on the tumor bearing mice along with drug delivery. After 36 days of treatment on these mice, ZnO-Gd-DOX nanoparticles greatly inhibited the tumor growth without causing any appreciable abnormality in major organs. The most important merit of ZnO-Gd-DOX was that such a nanoplatform was biodegraded completely and showed no toxic side effects after H&E (hematoxylin and eosin) staining of tumor slices and ICP-AES (inductively coupled plasma atomic emission spectrometry) bioanalyses.

Efficacy of dual-functional liposomes containing paclitaxel for treatment of lung cancer.

This study was mainly focused on the development of a dual-ligand liposomal delivery system for targeting the delivery of paclitaxel (PTX) to lung cancer. The specific ligand peptide HAIYPRH (T7) and the cationic cell-penetrating peptide TAT were connected with phospholipid via a polyethylene glycol (PEG) spacer to prepare the dual-ligand liposomes (T7/TAT-LP-PTX). Physicochemical characterizations of T7/TAT-LP-PTX, such as particle size, ζ potential, morphology, encapsulation efficiency, and in vitro PTX release, were also evaluated. In the cellular uptake study, the T7/TAT-LP endocytosed by the A549 cells was 2.26-, 3.48- and 8.56-fold higher than TAT-LP, T7-LP and LP, respectively. The IC50 values of TAT-LP-PTX, T7-LP-PTX and LP-PTX were much higher than those of T7/TAT-LP-PTX, respectively. The homing specificity of T7/TAT-LP was evaluated on the tumor spheroids, which revealed that T7/TAT-LP was more efficaciously internalized in tumor cells than TAT-LP, T7-LP and LP, respectively. Compared to LP, TAT-LP and T7-LP, T7/TAT-LP showed the strongest cell uptake property, and the highest accumulation ability in tumor spheroids in vitro. In the in vivo study, the T7/TAT-LP-PTX exhibited the best inhibitory effect of tumor growth for A549-bearing mice. Collectively, these results suggested that T7/TAT-LP-PTX is a promising drug delivery system for the treatment of lung cancer.

A novel solid-state electrochemiluminescence sensor for melamine with Ru(bpy)3(2+)/mesoporous silica nanospheres/Nafion composite modified electrode.

A novel melamine electrochemiluminescence (ECL) sensor was developed based on mesoporous SiO(2) nanospheres/Ru(bpy)(3)(2+)/Nafion modified electrodes. The homogeneous mesoporous silica nanospheres, synthesized using modified Stöber sol-gel process, were characterized by Field Emission Scanning Electron Microscopy (FE-SEM), Transmission Electron Microscopy (TEM) and Brunauer-Emmett-Teller (BET). The ECL and electrochemistry of the modified electrodes were investigated with tri-n-propylamine (TPA) as the coreactant. Furthermore, the mesporous SiO(2) nanospheres/Ru(bpy)(3)(2+)-based modified electrodes were used for ECL determination of melamine. The analytical performances of this ECL sensor for melamine based on its enhancement ECL emission of Ru(bpy)(3)(2+) were investigated. The results indicated that the sensor exhibited excellent performance during melamine determination with a wide linear range (7.81×10(-9)-5×10(-6) M), low detection limit (2.6×10(-9) M). The high sensitivity and stability mainly resulted from the high surface area and special structure of the mesoporous silica nanospheres. The proposed ECL approach was used to analyze the melamine content in powdered milk with satisfactory results.