Codelivery of miR-4638-5p and Docetaxel Based on Redox-Sensitive Polypeptide Micelles as an Improved Strategy for the Treatment of Castration-Resistant Prostate Cancer.

In this work, we have developed a reducible, self-assembling disulfide cross-linked and peptide-based micelle system for codelivery of miR-4638-5p and DTX to improve the efficacy of castration-resistant prostate cancer (CRPC) therapy. The result showed that DTX in micelles (DTX-VPs) inhibited cell growth and induced apoptosis more effectively than free DTX both in vitro and in vivo. In addition, the DTX and miR-4638-5p loaded micelles (Co-VPs) achieved the most pronounced anticancer effect of all groups. Immunohistochemical analysis indicated that miR-4638-5p in micelle system could effectively downregulate the expression of Kidins220 and further improve the anticancer effect by enhancing tumor cell apoptosis and suppressing tumor cell proliferation. Finally, the bioimaging analysis demonstrated that DIR in micelles (DIR-VPs) showed a higher concentration and a longer retention time in tumor tissue than did free DIR, which indicated an excellent tumor-targeting ability of the micelle system. All these results suggest that codelivery of miR-4638-5p and DTX via polypeptide micelle system has a potential for CRPC treatment.

Enhanced Systemic Anti-Angiogenic siVEGF Delivery Using PEGylated Oligo-d-arginine.

Angiogenesis mainly mediated by upregulation of vascular endothelial growth factor (VEGF) provides a hallmark of rapidly proliferating tumor cells and an essential component of the tumor growth and microenvironment, making it a targetable process for antitumor therapy. RNA interference (RNAi) provides a very effective tool for developing antitumor therapies; however, its application to date has been hampered due to the lack of efficient small interfering RNA (siRNA) delivery systems in vivo. Here, we report a polymeric gene carrier system based on PEGylation of a cationic cysteine-ended 9-mer arginine oligopeptide (CR9C), which provides effective siRNA systemic delivery and specifically suppresses VEGF (siVEGF). The PEG500-CR9C/siVEGF oligopeptoplex provided improved blood circulation, enhanced protection from serum proteases, reduced uptake in the liver and kidneys, enhanced tumor targeting, and down-regulated intratumoral VEGF level, which comprehensively resulted in improved antitumor efficacy without significant toxicity in vivo. PEG500-CR9C has a great potential for safe and efficient siRNA delivery with diverse applications.

White light-driven enhanced cerium-doped carbon dots activity to combat multidrug-resistant bacterial infection.

Infections caused by multidrug-resistant (MDR) bacteria are increasing and becoming an urgent global health crisis. The discovery and development of novel antibacterial agents to combat MDR are highly desirable. Here, we report the fabrication of cerium-doped carbon dots (CeCDs) with a simple hydrothermal method, which exhibit intrinsic broad efficacy against MDR bacteria including clinical isolates while maintaining low cytotoxicity and hemolytic effects. Importantly, the antibacterial activity of CeCDs is dramatically improved owing to the generation of reactive oxygen species (ROS) upon white light irradiation. Comprehensive analyses revealed that the CeCDs can penetrate the bacterial wall, disrupt the cell membrane, and prevent the biofilm formation, possibly hindering the bacterial resistance development. And the interaction of CeCDs with lipopolysaccharide (LPS) may contribute to the higher activity against Gram-negative bacteria strains. The treatment of CeCDs in a murine skin infection model can significantly reduce the number of bacteria on infected sites and accelerate wound healing by irradiation with light. Overall, CeCDs show great promise as low-cost and efficient antibacterial agents for chronic wounds and may be served as a powerful weapon to fight against the growing threat of MDR bacterial infection.

Synergistic Effect of WN/Mo2C Embedded in Bioderived Carbon Nanofibers: A Rational Design of a Shuttle Inhibitor and an Electrocatalyst for Lithium-Sulfur Batteries.

To improve the innate shuttle effect and the sluggish redox kinetics of lithium-sulfur batteries, a composite made of a bimetallic compound embedded in nitrogen-doped carbon nanofibers (CNFs) is synthesized by employing biomass collagen fibers (CFs) as a structure template. Metal anions WO42- and MoO42- are grafted on plant polyphenol-modified CFs and then in situ converted into WN/Mo2C implanted in a matrix of CNFs (WMCNFs). The obtained WN/Mo2C is of quantum size and uniform distribution, exposing the active sites maximally. Further, the heterostructure of the bimetallic composite enables unique electronic interaction, thereby synergistically enhancing its adsorption capability toward soluble intermediates and activating its catalytic function for liquid-liquid and liquid-solid conversions. Combining these merits, when used as a separator modification material and a sulfur host simultaneously, the WMCNFs composite exhibits remarkable cycling stability with 91.45% capacity retention after 500 cycles at 2 C and also prominent rate performance of delivering 552.75 mAh g-1 at a current rate of 10 C. Meanwhile, the stable luminescence operation of LED lights powered by the assembled pouch cell demonstrates the application potential of this biomaterial-derived composite.

Facile synthesis of the crescent-like SnS nanocrystals capped by polyvinyl pyrrolidone and its performance of adsorbing dyes.

With using Sn2+ as tin source, l-cysteine as sulphur source and polyvinyl pyrrolidone (PVP, Mw = 1300000) as surfactant, a novel three-dimensional and crescent-like SnS nanocrystal (NCs) was successfully synthesized in a one-pot hydrothermal method. The as-prepared SnS NCs displayed uniform crescent-like morphological structure, and demonstrated excellent efficiency for the adsorption of cationic dyes such as rhodamine B (RhB) and methylene blue (MB). Kinetic analysis indicated that the adsorption process followed the pseudo second-order model, and the maximum capacity of the SnS NCs to adsorb MB was determined by Langmuir equation to be 252 mg⋅g-1 at 298 K. The pH dependence of SnS NCs on the adsorption of cationic dyes and the characterization of zeta potential jointly suggested the existence of electrostatic attraction in the process. Overall, this study showed that electrostatic field of functional groups and the capping of PVP could significantly enhance the adsorption performance of the SnS NCs, and also provides a novel insight into the development of highly efficient inorganic adsorbents for cationic dyes.

Facile synthesis of novel three-dimensional Bi2S3 nanocrystals capped by polyvinyl pyrrolidone to enhance photocatalytic properties under visible light.

Exploitation of novel photocatalysts for highly efficient degradation of organic dyes and reduction of hexavalent chromium is of significance to reduce environmental pollution. Herein, a novel three-dimensional flower-like Bi2S3 nanocrystals composed of two-dimensional Bi2S3 nanosheets were prepared by one-pot hydrothermal method with polyvinyl pyrrolidone (Mw = 1300000) as a capping agent. The experimental results show that polyvinyl pyrrolidone has evident enhanced effect on the photocatalytic performance of Bi2S3, and the polyvinyl pyrrolidone modified three-dimensional Bi2S3 (Bi2S3-1) displays extraordinary catalytic activity for photodegradation of rhodamine B and photoreduction of Cr(VI) under visible light. The rates of photodegradating rhodamine B and photoreducing Cr(VI) with Bi2S3-1 can reach 93.9% in 30 min (k = 0.07675 min-1) and 95.2% in 5 min (k = 0.47351 min-1), respectively. The photocatalytic performance of polyvinyl pyrrolidone modified three-dimensional Bi2S3 is much better than those of previously reported bismuth-based nanostructures. This work provides a new insight into the development of inorganic photocatalysts for both degradation of organic dyes and reduction of heavy metal ions.

Bringing Psychological Strategies to Robot-Assisted Physiotherapy for Enhanced Treatment Efficacy.

Robotic technologies offer a range of functions to augment clinical rehabilitation practice. However, compliance with robot-assisted rehabilitation techniques has not been optimally achieved. Traditional approaches to improving the treatment efficacy are focusing more on the system function, while psychological factors have not been integrated comprehensively. In this perspective paper, eight key factors reflecting three conceptions-robot design, function design, and patients' expectations have been evaluated and analyzed. Clinical results with 28 therapists and 84 patients indicate that integrating psychological strategies into robot-assisted physiotherapy may promote better trust and acceptance of rehabilitation robots.

Surface States Induced Photoluminescence Enhancement of Nitrogen-Doped Carbon Dots Via Post-Treatments.

The tunable photoluminescence (PL) of nitrogen-doped carbon dots (NCDs) has attracted much attention in recent years while the specific mechanism is still in dispute. Herein, NCDs with yellow emission were successfully synthesized via a facile hydrothermal approach. Three kinds of post-treatment routes were investigated to verify the influence of surface states on the PL emission of NCDs including solvent-dependent, reduced-reaction and metal-enhanced effect. The interaction mechanism was studied by absorption spectrum, structural characterizations, steady-state and time-resolved spectroscopy. When dispersed in different solvents, the as-prepared NCDs show tunable emission and PL enhancement attributed to hydrogen bonding between solvents and NCDs. Besides, the addition of NaBH4 can induce the reduction of the C=O bonds existing in original NCDs to C-O bonds and thus result in the enhancement of the intrinsic (n-π*) emission. Moreover, metal-enhanced fluorescence of NCDs can also be observed when adding Ag+ into initial NCD solution, which might be ascribed to aggregation-induced emission enhancement. These results for post-treated NCDs demonstrate that surface functional groups are responsible for PL emission and provide new possibilities like multi-image sensing and lighting application.

Probing the Sulfur-Modified Capping Layer of Gold Nanoparticles Using Surface Enhanced Raman Spectroscopy (SERS) Effects.

Gold nanoparticles (AuNP) exhibit particular plasmonic properties when stimulated by visible light, which makes them a promising tool to many applications in sensor technology and biomedical applications, especially when associated to sulfur-based compounds. Sulfur species form a great variety of self-assembled structures that cap AuNP and this interaction rules the optical and plasmonic properties of the system. Here, we report the behavior of citrate-stabilized gold nanospheres in two distinct sulfur colloidal solutions, namely, thiocyanate and sulfide ionic solutions. Citrate-capped gold nanospheres were characterized using ultraviolet-visible (UV-Vis) absorption, transmission electron microscopy (TEM), energy dispersive spectroscopy (EDS), and atomic force microscopy (AFM). In the presence of sulfur species, we have observed the formation of NP clusters and chain-like structures, giving rise to surface-enhanced effects. Surface-enhanced Raman spectroscopy (SERS) pointed to a modification in citrate vibrational modes, which suggests substitution of citrate by either thiocyanate or sulfide ions with distinct dynamics, as showed by in situ fluorescence. Moreover, we report the emergence of surface-enhanced infrared absorption (SEIRA) effect, which corroborates SERS conclusions. Further, SEIRA shows a great potential as a tool for specification of sulfur compounds in colloidal solutions, which is particularly useful when dealing with sensor technology.

Diallyl Trisulfide Inhibits Growth of NCI-H460 in Vitro and in Vivo, and Ameliorates Cisplatin-Induced Oxidative Injury in the Treatment of Lung Carcinoma in Xenograft Mice.

Diallyl trisulfide (DATS), an organosulfuric component of garlic oil, exhibits potential anticancer and chemopreventive effects. Cisplatin (DDP), a common chemotherapeutic agent, has provided great therapeutic contributions to treating solid tumors, but with serious side effects. Here, we verified the anti-tumor properties of DATS on lung cancer in vitro and in vivo, and evaluated synergistic effects of DATS combined with DDP on the NCI-H460 xenograft model. Significantly decreased cell viabilities, cell cycle G1 arrest, and apoptosis induction were observed in DATS treated NCI-H460 cells (p<0.05). And injection of DATS (30 or 40 mg/kg) to female Balb/c mice significantly inhibited the growth of human NCI-H460 cell tumor xenograft (p<0.001). Moreover, DATS in combination with DDP exhibited enhanced anti-tumor activity via induction of apoptosis. Apoptosis pathways were confirmed by modulation of p53, Bcl-2 family members; induction of active caspase-3/8/9 and activation of JNK- and p38-MAPK pathways. Interestedly, DATS+DDP administration exerted fewer side effects, such as suppressing the weight loss and ameliorating DDP-induced oxidative injury, especially in renal parenchyma. In addition, increased E-cadherin and decreased MMP-9 expression levels were observed in DATS-treated tumor tissues. These studies provide supports that DATS might be a potential candidate for combination with DDP in cancer treatment.

Au/TiO2 Hollow Spheres with Synergistic Effect of Plasmonic Enhancement and Light Scattering for Improved Dye-Sensitized Solar Cells.

Au-decorated TiO2 hollow spheres (Au-THS) have been successfully synthesized via a facile one-pot solvothermal method. The Au-THS hybrid features unique hollow structure with a large specific surface area of 120 m2 g-1 and homogeneous decoration of Au nanoparticles, giving rise to enhanced light harvesting and charge generation/separation efficiency. When incorporated into the active layer of dye-sensitized solar cells (DSSCs), an improved power conversion efficiency of 7.3% is obtained, which is increased by 37.7% compared with the controlled P25 DSSC. The underlying mechanism to rationalize the efficiency enhancement can be mainly attributed to the strong synergistic effect of superior light scattering ability of the THS and the plasmonic-enhanced effect rendered by the Au nanoparticles.

Gold Nanoparticles Deposited Polyaniline-TiO2 Nanotube for Surface Plasmon Resonance Enhanced Photoelectrochemical Biosensing.

A novel ternary composite composed of TiO2 nanotubes (TiONTs), polyaniline (PANI), and gold nanoparticles (GNPs) was prepared for photoelectrochemical (PEC) biosensing. PANI was initially coated on TiONTs with an oxidative polymerization method, and 12-phosphotungstic acid was then used as a highly localized photoactive reducing agent to deposit GNPs on TiONT-PANI. The morphology and composition of the composite were characterized by various spectroscopic and microscopic methods. Electrochemical impedance spectroscopy was also conducted to demonstrate the excellent electrical conductivity of the composite. A PEC biosensor was fabricated by immobilizing a mixture of lactate dehydrogenase and the composite onto ITO electrodes, which regenerated nicotinamide adenine dinucleotide (NAD(+)) to complete the enzymatic cycle and led to an improved method for PEC detection of lactate. Because of the surface plasmon resonance enhanced effect of GNPs, the electrochromic performance of PANI, and excellent conductivity and biocompatibility of the composite, this method showed a dynamic range of 0.5-210 µM, sensitivity of 0.0401 µA µM(-1), and a detection limit of 0.15 µM.

Iontophoretic transport kinetics of ketorolac in vitro and in vivo: demonstrating local enhanced topical drug delivery to muscle.

The objective of the study was to investigate the iontophoretic delivery kinetics of ketorolac (KT), a highly potent NSAID and peripherally-acting analgesic that is currently indicated to treat moderate to severe acute pain. It was envisaged that, depending on the amounts delivered, transdermal iontophoretic administration might have two distinct therapeutic applications: (i) more effective and faster local therapy with shorter onset times (e.g. to treat trauma-related pain/inflammation in muscle) or (ii) a non-parenteral, gastrointestinal tract sparing approach for systemic pain relief. The first part of the study investigated the effect of experimental conditions on KT iontophoresis using porcine and human skin in vitro. These results demonstrated that KT electrotransport was linearly dependent on current density - from 0.1875 to 0.5mA/cm(2) - (r(2)>0.99) and drug concentration - from 5 to 20mg/ml (r(2)>0.99). Iontophoretic permeation of KT from a 2% hydroxymethyl cellulose gel was comparable to that from an aqueous solution with equivalent drug loading (584.59±114.67 and 462.05±66.56µg/cm(2), respectively). Cumulative permeation (462.05±66.56 and 416.28±95.71µg/cm(2)) and steady state flux (106.72±11.70 and 94.28±15.47µg/cm(2)h), across porcine and human skin, were statistically equivalent confirming the validity of the model. Based on the results in vitro, it was decided to focus on topical rather than systemic applications of KT iontophoresis in vivo. Subsequent experiments, in male Wistar rats, investigated the local enhancement of KT delivery to muscle by iontophoresis. Drug biodistribution was assessed in skin, in the biceps femoris muscle beneath the site of iontophoresis ('treated muscle'; TM), in the contralateral muscle ('non-treated muscle'; NTM) and in plasma (P). Passive topical delivery and oral administration served as negative and positive controls, respectively. Iontophoretic administration for 30min was superior to passive topical delivery for 1h and resulted in statistically significant increases in KT levels in the skin (91.04±15.48 vs. 20.16±8.58µg/cm(2)), in the biceps femoris at the treatment site (TM; 6.74±3.80 vs.