Enhanced photodynamic therapy of mixed phase TiO2（B）/anatase nanofibers for killing of HeLa cells

Photodynamic therapy （PDT）, which is a procedure that uses photosensitizing drug to apply therapy selectively to target sites, has been proven to be a safe treatment for cancers and conditions that may develop into cancers. Nano-sized TiO2 has been regarded as potential photosensitizer for UV light driven PDT. In this study, four types of TiO2 nanofibers were prepared from proton tri-titanate （H2T3O7） nanofiber. The as-obtained nanofibers were demonstrated as efficient photosensitizers for PDT killing of HeLa cells. MTT assay and flow cytometry （FCM） were carried out to evaluate the biocompatibility, percentage of apoptotic cells, and cell viability. The non-cytotoxicity of the as-prepared TiO2 nanofibers in the absence of UV irradiation has also been demonstrated. Under UV light irradiation, the TiO2 nanofibers, particularly the mixed phase nanofibers, displayed much higher cell-killing efficiency than Pirarubicin （THP）, which is a common drug to induce the apoptosis of HeLa cells. We ascribe the high cell- killing efficiency of the mixed phase nanofibers to the bandgap edge match and stable interface between TiO2（B） and anatase phases in a single nanofiber, which can inhibit the recombination of the photogenerated electrons and holes. This promotes the charge separation and transfer processes and can produce more reactive oxygen species （ROS） that are responsible for the killing of HeLa cells.     

Catalase-imprinted Fe<Subscript>3</Subscript>O<Subscript>4</Subscript>/Fe@fibrous SiO<Subscript>2</Subscript>/polydopamine nanoparticles: An integrated nanoplatform of magnetic targeting,magnetic resonance imaging,and dual-mode cancer therapy

Recent advances in the research on the molecular mechanism of cell death and methods for preparation of nanomaterials make the integration of various therapeutic approaches,targeting,and imaging modes into a single nanoscale complex a new trend for the development of future nanotherapeutics.Hence,a novel ellipsoidal composite nanoplatform composed of a magnetic Fe3O4/Fe nanorod core (～120 nm) enwrapped by a catalase (CAT)-imprinted fibrous SiO2/ polydopamine (F-SiO2/PDA) shell with thickness 70 nm was prepared in this work.In vitro experiments showed that the Fe3O4/Fe@F-SiO2/PDA nanoparticles can selectively inhibit the bioactivity of CAT in tumor cells by the molecular imprinting technique.As a result,the H2O2 level in tumor cells was elevated dramatically.At the same time,the Fe3O4/Fe core released Fe ions to catalyze the conversion of H2O2 to ·OH in tumor cells.Eventually,the concentration of ·OH in tumor cells rapidly rose to a lethal level thus triggering apoptosis.Combined with the remarkable near-infrared light (NIR) photothermal effect of the CATimprinted PDA layer,the Fe3O4/Fe@F-SiO2/PDA nanoparticles can effectively kill MCF-7,HeLa,and 293T tumor cells but are not toxic to nontumor cells.Furthermore,these nanoparticles show good capacity for magnetic targeting and suitability for magnetic resonance imaging (MRI).Therefore,the integrated multifunctional nanoplatform opens up new possibilities for high-efficiency visual targeted nonchemo therapy for cancer.     

Presentation matters: Identity of gold nanocluster capping agent governs intracellular uptake and cell metabolism

Au nanoclusters （AuNCs） hold tremendous potential to be employed in a wide variety of biological applications. Despite the rapid development in the field of NCs synthesis, a comprehensive understanding of how cells interact with this class of ultra-small nanoparticles （〈2 nm） having defined sizes and surface chemistry, remains poorly understood. In this study, we show that the choice of the surface ligand used to protect AuNCs can significantly perturb cellular uptake and intracellular redox signaling. A panel of monodisperse, atomically precise AuNCs with different core Au atom number （i.e., Auls, Au18 and Au25） protected with either mercaptopropionic acid （MPA） or glutathione （GSH） capping agent were synthesized and their effects on the generation of intracellular reactive oxygen species （ROS）, cytotoxicity and genotoxicity of the NCs were assessed. Both mitochondrial superoxide anion （O2^-） and cytoplasmic ROS were found to be higher in cells exposed to MPA but not GSH capped AuNCs. The unregulated state of intracellular ROS is correlated to the amount of internalized AuNCs. Interestingly, MPA-AuNCs induction of ROS level did not lead to any detrimental cellular effects such as cell death or DNA damage. Instead, it was observed that the increase in redox status corresponded to higher cellular metabolism and proliferative capacity. Our study illustrates that surface chemistry of AuNCs plays a pivotal role in affecting the biological outcomes and the new insights gained will be useful to form the basis of defining specific design rules to enable rational engineering of ultra-small complex nanostructures for biological applications.     

The associated killing of hepatoma cells using multilayer drug-loaded mats combined with fast neutron therapy

Chemotherapeutic and radiation therapy have emerged as two most important treatment strategies to treat cancer in clinical practice;however,to improve anticancer efficacy,combination chemotherapy still remains challenge.Dichloroacetate(DCA)could produce significant cytotoxic effects in certain tumor cells through its distinct mechanism.Radiation therapy with fast neutrons(FNT)has high relative biolgical effectiveness compared to other radiotherapeutics.Herein,we reported the combination chemotherapy with FNT for effective tumor growth inhibition with the assistance of a multilayered nanofiber loading DCA and DCA derivatives.We first synthesized a biodegradable polylysine to condense DCA with negative charge,or to conjugate DCA by condensing synthesis,to obtain Ion-DCA and Co-DCA,respectively.DCA,Ion-DCA or Co-DCA was then loaded into fibers to form multilayer drug-loaded mats.Upon adhesion on the surface of subcutaneous and orthotopic liver tumors,the multilayer drug-loaded mats realized a controllable release of DCA,which reversed the Warburg effect and inhibited cancer cell proliferation.Meantime,irradiation of fast neutrons could seriously damage DNA structure.Combination of the controllable release of DCA and FNT resulted in synergistic cell apoptosis in vitro,and the tumor inhibition in vivo.This study thus provides a new approach to integrate chemotherapy and FNT with the assistance of biocompatible nanofiber for synergistic tumor therapy.     

Hot-nanoparticle-mediated fusion of selected cells

Complete fusion of two selected cells allows for the creation of novel hybrid cells with inherited genetic properties from both original cells.Alternatively,via fusion of a selected cell with a selected vesicle,chemicals or genes can be directly delivered into the cell of interest,to control cellular reactions or gene expression.Here,we demonstrate how to perform an optically controlled fusion of two selected cells or of one cell and one vesicle.Fusion is mediated by laser irradiating plasmonic gold nanoparticles optically trapped between two cells (or a vesicle and a cell) of interest.This hot-particle-mediated fusion causes total mixing of the two cytoplasms and the two cell membranes resulting in formation of a new hybrid cell with an intact cell membrane and enzymatic activity following fusion.Similarly,fusion between a vesicle and a cell results in delivery of the vesicle cargo to the cytoplasm,and after fusion,the cell shows signs of viability.The method is an implementation of targeted drug delivery at the single-cell level and has a great potential for cellular control and design.     

Regulation of pathological BBB restoration via nanostructured ROS-responsive glycolipid-like copolymer entrapping siVEGF for glioblastoma targeted therapeutics

Glioblastoma(GBM)is one of the malignant brain tumors with high mortality and no curative treatments.Abnormally elevated vascular endothelial growth factor(VEGF)in GBM seriously disrupts the blood brain barrier(BBB)with an increased permeability,resulting in poor outcome and prognosis.RNAi interference has shown strong potential to inhibit VEGF expression,thus it is necessary to development an effective and safe gene delivery system possessing the ability to cross the BBB and target GBM cells.This study aims to explore the anti-GBM effect of angiopep-2(Ap)peptide modified reactive oxygen species(ROS)cleavable thioketal(TK)linked glycolipid-like nanocarrier(CSTKSA)delivering anti-VEGF siRNA(R),termed as Ap-CSTKSA/R complexes.Ap functionalized modification produced an enhanced cellular uptake and a stronger bio-distribution of Ap-CSTKSA/R complexes in U87 MG cells and brain tumor tissues,respectively.Ap-CSTKSA/R complexes exhibited great superiority in GBM growth inhibition and finally translated into the longest survival period mainly via receptor-mediated targeting delivery,VEGF gene silencing accompanied with remarkable angiogenesis inhibition,and suppressed expression of caveolin-1 which is involved in BBB functional regulation in the occurrence and treatment of GBM.The study indicated that Ap functionalization on ROS-responsive glycolipid-like copolymer exhibits a promising and effective gene delivery platform for GBM targeted treatment.     

Glucose-conjugated chitosan nanoparticles for targeted drug delivery and their specific interaction with tumor cells

A novel targeted drug delivery system, glucose-conjugated chitosan nanoparticles （GCNPs）, was developed for specific recognition and interaction with glucose transporters （Gluts） over-expressed by tumor cells. GC was synthesized by using succinic acid as a linker between glucosamine and chitosan （CS）, and successful synthesis was confirmed by NMR and elemental analysis. GCNPs were prepared by ionic crosslinking method, and characterized in terms of morphology, size, and zeta potential. The optimally prepared nanoparticles showed spherical shapes with an average particle size of （187.9 ± 3.8） nm and a zeta potential of （-15.43 ± 0.31） mV. The GCNPs showed negligible cytotoxicity to mouse embryo fibroblast and 4T1 cells. Doxorubicin （DOX） could be efficiently entrapped into GCNPs, with a loading capacity and encapsulation efficiency of 20.11% and 64.81%, respectively. DOX-Ioaded nanoparticles exhibited sustained-release behavior in phosphate buffered saline （pH 7.4）. In vitro cellular uptake studies showed that the GCNPs had better endocytosis ability than CSNPs, and the antitumor activity of DOX/GCNPs was 4-5 times effectiveness in 4T1 cell killing than that of DOX/CSNPs. All the results demonstrate that nanoparticles decorated with glucose have specific interactions with cancer cells via the recognition between glucose and Gluts. Therefore, Gluts-targeted GCNPs may be promising delivery agents in cancer therapies.     

Structural and Optoelectronic Properties of Nanostructured ITO Thin Films Deposited by Chemical Spray Pyrolysis Technique

In this study, the spray pyrolysis method is used to generate an indium tin oxide （ITO） thin film on a glass substrate. In2O3 layers were deposited and doped with tin at different doping concentration ranging from 2% to 6%. ITO thin films for application in thin-film silicon solar cells with superior structure and optical properties （grain size ranging from 44 to 84 nm; transparency of〉 87%） have been investigated. This investigation elucidates the properties of ITO thin films used as antireflection front electrodes in p-n j unction Si solar cells. Microstructure, surface morphology, optoelectrical and optical properties of these films were then characterized and analyzed. Next, the effects of doping concentration of ITO film growth were discussed. The ITO thickness was optimized considering that the refractive index of Si emitter layer optimizes its optical characteristics and p-n junction solar cell spectral response. The best increasing in p-n junction solar cell conversion efficiency was 4% with an open circuit voltage （Voc） of 0.425 V, fill factor （FF） of 0.47, and short circuit current density （Jsc） of 0.91 mA/cm2.     

Biocompatibility of iron carbide and detection of metals ions signaling proteomic analysis via HPLC/ESI-Orbitrap

Recently,magnetic nanoparticles (NPs) have been extensively used in food industry and biomedical treatments.However,the biocompatibility mechanism on expression proteomics,before consideration of magnetic NPs for clinical application,has not yet been fully elucidated.Therefore,this study was undertaken to identify potential biomarkers of metal ion signaling proteins in human cervical cancer cell line (HeLa) cells.Here,we report the in vitro investigations of the cell cycle response and significant changes in protein abundance of HeLa cells when exposed to self-tailored hydrophilic Fe2C NPs.The comparative proteomic approach based on 18O labeling coupled with high performance liquid chromatography/electrospray ionization with ion trap mass analyzer (HPLC/ESI-Orbitrap) was applied,and 394 proteins were identified.There were 46 significantly differentiated proteins based on the specific metal ion signaling response.Among them,60S ribosomal protein L37a,serine/arginine-rich splicing factor 7,calmodulin,and calumenin were downregulated,whereas transketolase was overexpressed.Functional interaction network of Fe2C-regulated proteins was successfully created by the STRING algorithm to show the strong interactions between proteins.This work will not only help to understand the molecular mechanism of metal ion signaling proteins that can potentially be used to develop therapeutic protocols for diagnosis of diseases but also give direction for tailoring biocompatible magnetic NPs.     

Anti Cervix Cancer Activity of Co-immobilized Tumor Necrosis Factor-α and Interferon-γ

Tumor necrosis factor α （TNF-α） and interferon-γ （IFN-γ） are cytokines with strong antitumor activities. They were reacted with a photoactive arylazide-4-azidobenzoic acid, resulting in photoactive TNF-α and IFN-γ. The infrared （IR） spectra of these products showed the characteristic absorption of an azido group at 2127 cm^-1. By photo-immobilization, this modified TNF-α and IFN-γ were immobilized on polystyrene membranes for cell culture to prepare biomaterials. The micro-morphology of photoactive cytokines was observed with a scanning electron microscope （SEM）. The inhibitory effect on growth of Hela cells and inducing apoptosis activity of these two cytokines were analyzed by growth curve, transmission electron microscope （TEM） and fluorescence active cell sorter （FACS）. The results showed that co-immobilization of IFN-γ and TNF-α had significant inhibitory effect on growth of Hela cells, inhibitory rate up to 82%, and IFN-γ had obviously synergistic action.     

Upconversion nano-photosensitizer targeting into mitochondria for cancer apoptosis induction and cyt c fluorescence monitoring

Disruption of mitochondrial reactive oxygen species (mitoROS) plays a major role in cancer cell apoptosis. Here, we designed a core/shell-structured mitochondria-targeting upconversion-based nano-photosensitizer (TPP-UC(PS)) with a lanthanide-doped upconversion nanoparticle (UCNP) core coated by a photosensitizer (PS)-incorporated dense silica shell. Following irradiation with external near-infrared laser (NIR), TPP-UC(PS) in mitochondria caused serious mitochondrial matrix swelling for the activated upconversion-based photodynamic therapy (UC-PDT), and the mobilization of cytochrome c (cyt c) was amplified in response to the increased mitoROS. Specifically, this heme-containing cyt c could be monitored by varying TPP-UC(PS)’s upconversion luminescence signal (UCL), which may facilitate the in situ detection of cyt c for apoptosis research. As a proof of concept, our designed TPP-UC(PS) may provide significant opportunities for controlling cancer cell apoptosis under NIR stimulation and for studying apoptosis using the dynamic UCL, which is influenced by local cyt c.

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A novel tumor-targeting treatment strategy uses energy restriction via co-delivery of albendazole and nanosilver

Although nanotechnology has been rapidly developed and applied in tumor targeting, the outcome of chemotherapy remains greatly restricted by the toxicity of cytotoxic drugs in normal tissues and cells. Therefore, the development of alternative delivery systems, with few side effects in normal cells, has attracted increasing attention. Energy restriction is a novel and promising approach to cancer treatment, which can restrict tumor growth via inhibition of cellular energy metabolism. In this study, a novel tumor targeting system, based on folate-conjugated bovine serum albumin (BSA), was developed to co-deliver albendazole and nanosilver simultaneously, to restrain the energy metabolism of tumor cells. This nanosystem showed stronger anti-tumor efficacy than those using nanoparticles without folic acid modification, nanosilver, or albendazole, both in vitro and in vivo. This nanosystem depleted cellular ATP via direct inhibition of glycolytic enzymes and mitochondrial damage, resulting in inhibition of proliferation, cell-cycle arrest, and apoptosis of tumor cells. The enhanced anti-tumor activity contributed to the tumor-targeting ability of this system, resulting in specific energy inhibition in tumor cells. Toxicity evaluation was performed to confirm the safety of this system. This nanosystem provides an efficient and safe strategy for tumor therapy.

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Functionalization of high-moment magnetic nanodisks for cell manipulation and separation

Synthetic antiferromagnetic （SAF） nanoparticles are layer-structured particles with high single-particle magnetic moments. In order to covalently bind these nanopartides to cells, they were coated with a silica shell followed by conjugation with streptavidin. The silica coating generates both SAF@SiO2 core-shell nano- particles and silica core-free nanopartides. Using a simple magnetic separation, silica nanoparticles were removed and SAF@SiO2 nanoparticles were purified. After streptavidin conjugation, these particles were used to stain lung cancer cells, making them highly magnetically responsive. The stained cells can rotate in response to an external magnetic field and can be captured when a blood sample containing these cells flows through the sifter.     

Thickness-dependent patterning of MoS2 sheets with well-oriented triangular pits by heating in air

Patterning ultrathin MoS2 layers with regular edges or controllable shapes is appealing since the properties of MoS2 sheets are sensitive to the edge structures. In this work, we have introduced a simple, effective and well-controlled technique to etch layered MoS2 sheets with well-oriented equilateral triangular pits by simply heating the samples in air. The anisotropic oxidative etching is greatly affected by the surrounding temperature and the number of MoS2 layers, whereby the pit sizes increase with the increase of surrounding temperature and the number of MoS2 layers. First-principles computations have been performed to explain the formation mechanism of the triangular pits. This technique offers an alternative avenue to engineering the structure of MoS2 sheets.     

Solution-processable graphene mesh transparent electrodes for organic solar cells

Graphene mesh electrodes (GMEs) with good conductivity and transparency have been fabricated by the standard industrial photolithography and O₂ plasma etching process using graphene solutions. Organic photovoltaic (OPV) cells using GMEs as the transparent electrodes with a blend of poly-(3-hexylthiophene)/phenyl-C₆₁-butyric acid methyl ester (P3HT/PC₆₁BM) as the active layer have been fabricated and exhibit a power conversion efficiency (PCE) of 2.04%, the highest PCE for solution-processed graphene transparent electrode-based solar cells reported to date.      

Enhanced π-π interactions between a C60 fullerene and a buckle bend on a double-walled carbon nanotube

In situ low-voltage aberration corrected transmission electron microscopy (TEM) observations of the dynamic entrapment of a C₆₀ molecule in the saddle of a bent double-walled carbon nanotube is presented. The fullerene interaction is non-covalent, suggesting that enhanced π-π interactions (van der Waals forces) are responsible. Classical molecular dynamics calculations confirm that the increased interaction area associated with a buckle is sufficient to trap a fullerene. Moreover, they show hopping behavior in agreement with our experimental observations. Our findings further our understanding of carbon nanostructure interactions, which are important in the rapidly developing field of low-voltage aberration corrected TEM and nano-carbon device fabrication.      

Inhibitory activity of gold and silica nanospheres to vascular endothelial growth factor （VEGF）-mediated angiogenesis is determined by their sizes

Nanoparticles can be involved in biological activities such as apoptosis, angiogenesis, and oxidative stress by themselves. In particular, inorganic nanoparticles such as gold and silica nanoparticles are known to inhibit vascular endothelial growth factor （VEGF）-mediated pathological angiogenesis. In this study, we show that anti-angiogenic effect of inorganic nanospheres is determined by their sizes. We demonstrate that 20 nm size gold and silica nanospheres suppress VEGF-induced activation of VEGF receptor-2, in vitro angiogenesis, and in vivo pathological angiogenesis more efficiently than their 100 nm size counterparts. Our results suggest that modulation of the size of gold and silica nanospheres determines their inhibitory activity to VEGF-mediated angiogenesis.     

A nanoporous oxide interlayer makes a better Pt catalyst on a metallic substrate: Nanoflowers on a nanotube bed

To improve the contact between platinum catalyst and titanium substrate, a layer of TiO2 nanotube arrays has been synthesized before depositing Pt nanoflowers by pulse electrodeposition. Dramatic improvements in electrocatalytic activity （3x） and stability （60x） for methanol oxidation were found, suggesting promising applications in direct methanol fuel cells. The 3x and 60x improvements persist for Pt/Pd catalysts used to overcome the CO poisoning problem.     

Synthesis and characterization of WS2 inorganic nanotubes with encapsulated/intercalated CsI

WS₂ nanotubes have been filled and intercalated by molten phase caesium iodide. The presence of caesium iodide inside the WS₂ nanotubes has been determined using high-resolution transmission electron microscopy (HRTEM) coupled with electron energy-loss spectroscopy (EELS) and energy-dispersive X-ray spectroscopy (EDS). Noticeably, a Moiré pattern was observed due to the interference between encapsulated CsI and WS₂ layers. The intercalation of CsI into the host concentric WS₂ lattices resulted in an increase in the interplanar spacing.      

Superhydrophobic and antireflective nanograss-coated glass for high performance solar cells

We present a facile method for producing superhydrophobic nanograss-coated （SNGC） glass surfaces that possess both reduced reflectivity and self-cleaning properties at the air/glass interface. The refractive index of a CaF2 nanograss （NG） layer on a glass substrate, deposited by glancing angle vapor deposition, is 1.04 at 500 nm, which is the second-lowest value ever reported so far. The fluorinated NG layer gives rise to a high water contact angle （〉150°） and very efficient cleaning out of dust with water drops. Using the dual functionalities of the SNGC glass, we demonstrate superhydrophobic and antireflective organic photovoltaic cells with excellent power conversion efficiency.