A Near-Infrared Light-Activated Photocage Based on a Ruthenium Complex for Cancer Phototherapy.

Conventional photocages only respond to short wavelength light, which is a significant obstacle to developing efficient phototherapy in vivo. The development of photocages activated by near-infrared (NIR) light at wavelengths from 700 to 950 nm is important for in vivo studies but remains challenging. Herein, we describe the synthesis of a photocage based on a ruthenium (Ru) complex with NIR light-triggered photocleavage reaction. The commercial anticancer drug, tetrahydrocurcumin (THC), was coordinated to the RuII center to create the Ru-based photocage that is readily responsive to NIR light at 760 nm. The photocage inherited the anticancer properties of THC. As a proof-of-concept, we further engineered a self-assembled photocage-based nanoparticle system with amphiphilic block copolymers. Upon exposure to NIR light at 760 nm, the Ru complex-based photocages were released from the polymeric nanoparticles and efficiently inhibited tumor proliferation in vivo.

Tipping Gold Nanobipyramids with Titania for the Use of Plasmonic Hotspots to Drive Amine Coupling.

Designing plasmonic photocatalysts with spatially controlled catalytic sites is an effective strategy to boost the sunlight-driven chemical transformation efficiency through plasmonic enhancement. Herein, we describe a facile method for the synthesis of TiO2-tipped Au nanobipyramids (NBPs) to give (Au NBP)/t-TiO2 nanodumbbells. The surfactant cetyltrimethylammonium bromide concentration is the key factor in the construction of this type of unique nanostructure. The photocatalytic aerobic oxidative coupling of amines using the plasmonic photocatalysts with the dumbbell-like and core@shell structures indicates that the TiO2-tipped ends for the photo-reduction and the exposed adjacent Au surface for the photo-oxidation on (Au NBP)/t-TiO2 can significantly improve the photocatalytic activity. The underlying mechanism of the photocatalytic oxidative coupling of benzylamine over (Au NBP)/t-TiO2 has been thoroughly investigated. Both experimental and simulation results for (Au NBP)/t-TiO2 and (Au nanorod)/t-TiO2 confirm the important effect of the plasmonic hotspots on the enhancement of the photocatalytic activity.

Bioinspired Synthesis of ZnO@polydopamine/Au for Label-Free Photoelectrochemical Immunoassay of Amyloid-ß Protein.

Amyloid-ß protein (Aß) is an important biomarker and plays a key role in the early stage of Alzheimer's disease (AD). Here, an ultrasensitive photoelectrochemical (PEC) sensor based on ZnO@polydopamine/Au nanocomposites was constructed for quantitative detection of Aß. In this sensing system, the ZnO nanorod array decorated with PDA films and gold nanoparticles (Au NPs) have excellent visible-light activity. The PDA film was used as a sensitizer for charge separation, and it also was used for antibody binding. Moreover, Au NPs were loaded on the surface of PDA film by in situ deposition, which further improved the charge transfer efficiency and the PEC activity in visible light due to the localized surface plasmon resonance effect of Au NPs. Therefore, in ZnO@polydopamine/Au nanocomposites, a significantly enhanced photocurrent response was obtained on this photoelectrode, which provides a good and reliable signal for early detection of AD. Under the optimized conditions, the PEC immunosensor displayed a wide linear range from 1 pg/mL to 100 ng/mL and a low detection limit of 0.26 pg/mL. In addition, this PEC immunosensor also presented good selectivity, stability, and reproducibility. This work may provide a promising point-of-care testing method toward advanced PEC immunoassays for AD biomarkers.

A Sequential Dual-Model Strategy Based on Photoactivatable Metallopolymer for On-Demand Release of Photosensitizers and Anticancer Drugs.

The synergistic combination of chemotherapy and photodynamic therapy has attracted considerable attention for its enhanced antitumoral effects; however, it remains challenging to successfully delivery photosensitizers and anticancer drugs while minimizing drug leakage at off-target sites. A red-light-activatable metallopolymer, Poly(Ru/PTX), is synthesized for combined chemo-photodynamic therapy. The polymer has a biodegradable backbone that contains a photosensitizer Ru complex and the anticancer drug paclitaxel (PTX) via a singlet oxygen (1 O2 ) cleavable linker. The polymer self-assembles into nanoparticles, which can efficiently accumulate at the tumor sites during blood circulation. The distribution of the therapeutic agents is synchronized because the Ru complex and PTX are covalently conjugate to the polymer, and off-target toxicity during circulation is also mostly avoided. Red light irradiation at the tumor directly cleaves the Ru complex and produces 1 O2 for photodynamic therapy. Sequentially, the generated 1 O2 triggers the breakage of the linker to release the PTX for chemotherapy. Therefore, this novel sequential dual-model release strategy creates a synergistic chemo-photodynamic therapy while minimizing drug leakage. This study offers a new platform to develop smart delivery systems for the on-demand release of therapeutic agents in vivo.

Research Progress of Oxygen Evolution Reaction Catalysts for Electrochemical Water Splitting.

The development of a low-cost and high-efficiency oxygen evolution reaction (OER) catalyst is essential to meet the future industrial demand for hydrogen production by electrochemical water splitting. Given the limited reserves of noble metals and many competitive applications in environmental protection, new energy, and chemical industries, many studies have focused on exploring new and efficient non-noble metal catalytic systems, improving the understanding of the OER mechanism of non-noble metal surfaces, and designing electrocatalysts with higher activity than traditional noble metals. This Review summarizes the research progress of anode OER catalysts for hydrogen production by electrochemical water splitting in recent years, for noble metal and non-noble metal catalysts, where non-noble metal catalysts are highlighted. The categories are as follows: (1) Transition metal-based compounds, including transition metal-based oxides, transition metal-based layered hydroxides, and transition metal-based sulfides, phosphides, selenides, borides, carbides, and nitrides. Transition metal-based oxides can also be divided into perovskite, spinel, amorphous, rock-salt-type, and lithium oxides according to their different structures. (2) Carbonaceous materials and their composite materials with transition metals. (3) Transition metal-based metal-organic frameworks and their derivatives. Finally, the challenges and future development of the OER process of water splitting are discussed.

Cancer immunogenic cell death via photo-pyroptosis with light-sensitive Indoleamine 2,3-dioxygenase inhibitor conjugate.

Immune checkpoint blockade (ICB) therapy currently considered as to be effective way to cure cancer in clinic. However, the insufficient tumor immunogenicity and the immunosuppressive tumor microenvironment always result in diminished efficacy of immunotherapy. Herein, we report the synthesis of an organic photo-immune activator NBS-1MT, the combination of photosensitizer and Indoleamine 2,3-dioxygenase (IDO) inhibitor effectively stimulates lysosomes oxidative stress the releases inflammatory cytokines. This process triggers pyroptosis for the considerable immunogenic cell death (ICD) while reversing suppressive tumor microenvironment. The photo-immune drug shows outstanding potential to activate caspase-1and then remove gasdermin-D (GSDMD), which could stimulate pyroptosis and also inhibit the tumor growth successfully in both primary and distant tumor. Furthermore, pyroptosis activated by photodynamic therapy (PDT) promotes the immune related factors release, and enhance the intratumoral infiltration of cytotoxic T lymphocytes (CTLs) with the induction of ICD of tumor cells and the cascaded synergize with IDO inhibitor, so the general antitumor immune response could be strengthened effectively. Our research confirms that the use of NBS-1MT is a promising strategy to boost the immune response and eventually to inhibit tumor growth.

Red-Light-Responsive Ru Complex Photosensitizer for Lysosome Localization Photodynamic Therapy.

Photoresponsive ruthenium (Ru) complexes have been extensively studied in the photodynamic therapy (PDT) of cancer. The metal-to-ligand charge transfer (MLCT) absorption maximum of most Ru complexes is located in the short-wavelength visible region, which is well suited for superficial tumors but shows inefficient therapeutic effects for more deep-seated ones. Moreover, Ru complexes are primarily located in the mitochondria or nucleus, always resulting in high levels of dark toxicity and DNA mutation. Herein, we reported a new ruthenium complex (Ru-I) for red-light-triggered PDT. The activation wavelength of Ru-I is successfully extended to 660 nm. Importantly, the complex photosensitizer can be quickly taken up by cancer cells and selectively accumulated in the lysosome, an ideal localization for PDT purposes. Intratumoral injection of Ru-I into tumor-bearing mice achieved excellent therapeutic effects and thus holds great promise for applications in lysosome localization photodynamic therapy.

Electrochemical immunosensor based on AuBP@Pt nanostructure and AuPd-PDA nanozyme for ultrasensitive detection of APOE4.

An ultrasensitive sandwich-type electrochemical immunosensor based on AuBP@Pt nanostructures and AuPd-PDA nanozyme was developed for the detection of apolipoprotein E4 (APOE4) which was an important risk factor for Alzheimer's disease (AD). In this work, gold nanobipyramid coated Pt (AuBP@Pt) nanostructures were prepared and applied to electrochemical immunosensors as a substrate material. AuBP@Pt nanostructures have advantages of electrical conductivity and large electroactive area, which could greatly increase electron transfer rate. In previous work, we designed AuPd alloy modified polydopamine (AuPd-PDA) nanozyme which catalyzed the decomposition of hydrogen peroxide (H2O2). AuPd-PDA nanozyme was used to label detection antibody due to excellent catalytic capability and stability in this new paper. And the concentration of APOE4 could be detected quantitatively by variation for transient current. As a result, the electrochemical immunosensor based on AuBP@Pt and AuPd-PDA exhibited a wide linear range from 0.05 to 2000 ng mL-1 and low detection limit of 15.4 pg mL-1 (S/N = 3). Furthermore, the designed biosensor displayed good selectivity in phosphate buffer saline (PBS) buffer solution or commercial goat serum, which provided a promising tool for early diagnosis of AD.

Titania-coated 2D gold nanoplates as nanoagents for synergistic photothermal/sonodynamic therapy in the second near-infrared window.

The development of efficient nanomedicines to improve anticancer therapeutic effects is highly attractive. In this work, we firstly report titania-coated Au nanoplate (Au NPL@TiO2) heterostructures, which play dual roles as nanoagents for synergistic photothermal/sonodynamic therapy in the second near-infrared (NIR) window. On the one hand, because the controlled TiO2 shells endow the Au NPL@TiO2 nanostructures with a red shift to the NIR II region, the as-prepared Au NPL@TiO2 nanostructures possess a high photothermal conversion efficiency of 42.05% when irradiated by a 1064 nm laser and are anticipated to be very promising candidates as photothermal agents. On the other hand, the Au nanoplates (Au NPLs), as electron traps, vastly improve the generation of reactive oxygen species (ROS) by the Au NPL@TiO2 nanostructures in contrast with pure TiO2 shell nanoparticles upon activation by ultrasound (US) via a sonodynamic process. Moreover, the toxicity and therapeutic effect of the Au NPL@TiO2 nanostructures were relatively systemically evaluated in vitro. The Au NPL@TiO2 nanostructures generate a large amount of intracellular ROS and exhibit laser power density-dependent toxicity, which eventually induces apoptosis of cancer cells. Furthermore, a synergistic therapeutic effect, with a cell viability of only 20.3% upon both photothermal and sonodynamic activation, was achieved at low concentrations of the Au NPL@TiO2 nanostructures. Experiments on mice also demonstrate the superiority of the combination of PTT and SDT, with the total elimination of tumors. This work provides a way of applying two-dimensional (2D) gold nanoplate core/TiO2 shell nanostructures as novel nanoagents for advanced multifunctional anticancer therapies in the second NIR window.

Hydrogen storage in Mg2Ni(Fe)H4 nano particles synthesized from coarse-grained Mg and nano sized Ni(Fe) precursor.

In this work, Mg2Ni(Fe)H4 was synthesized using precursors of nano Ni(Fe) composite powder prepared through arc plasma method and coarse-grained Mg powder. The microstructure, composition, phase components and the hydrogen storage properties of the Mg-Ni(Fe) composite were carefully investigated. It is observed that the Mg2Ni(Fe)H4 particles formed from the Mg-Ni(Fe) composite have a diameter of 100-240 nm and a portion of Fe in the Ni(Fe) nano particles transformed into α-Fe nano particles with the diameter of 40-120 nm. DSC measurements showed that the peak desorption temperature of the Mg2Ni(Fe)H4 was reduced to 501 K and the apparent activation energy for hydrogen desorption of the Mg2Ni(Fe)H4 was 97.2 kJ mol-1 H2. The formation enthalpy of Mg2Ni(Fe)H4 was measured to be -53.1 kJ mol-1 H2. The improvements in hydrogen sorption kinetics and thermodynamics can be attributed to the catalytic effect from α-Fe nano particles and the destabilization of Mg2NiH4 caused by the partial substitution of Ni by Fe, respectively.

Spontaneous interfacial reaction between metallic copper and PBS to form cupric phosphate nanoflower and its enzyme hybrid with enhanced activity.

We herein report the spontaneous interfacial reaction between copper foil with 0.01 M phosphate buffered saline (PBS) to form free-standing cupric phosphate (Cu3(PO4)2) nanoflowers at ambient temperature. The underlying chemistry was thoroughly investigated and it is found that the formation of nanoflower is synergistically caused by dissolved oxygen, chlorine ions and phosphate ions. Enzyme-Cu3(PO4)2 hybrid nanoflower was further prepared successfully by using an enzyme-dissolving PBS solution and the enzymes in the hybrid exhibit enhanced biological activity. This work provides a facile route for large-scale synthesis of hierarchical inorganic and functional protein-inorganic hybrid architectures via a simple one-step solution-immersion reaction without using either template or surfactant, thus offering great potential for biosensing application among others.

Sensitive detection of multiple mycotoxins by SPRi with gold nanoparticles as signal amplification tags.

Detection of multiple toxic mycotoxins is of importance in food quality control. Surface plasmon resonance imaging (SPRi) is an advanced tool for simultaneously multiple detections with accuracy; however, it suffers from limited sensitivity due to the instrumental constraint and small sizes of mycotoxins with only one epitope for an insensitive competitive immunoassay. In this work a gold nanoparticle (AuNP)-enhanced SPRi chip is designed to sensitively detect multiple mycotoxins using a competitive immunoassay format. The sensing surface is constructed by uniformly attaching dense mycotoxin antigens on poly[oligo(ethylene glycol) methacrylate-co-glycidyl methacrylate] (POEGMA-co-GMA) brush modified SPRi gold chip. After competitive binding in a sample solution containing respective monoclonal antibodies, secondary antibody-conjugated AuNPs are employed to bind with the captured monoclonal antibodies for further amplification of the SPRi signal. Highly specific and sensitive simultaneous detection is achieved for three typical mycotoxins including Aflatoxin B1 (AFB1), Ochratoxin A (OTA) and Zearalenone (ZEN) with low detection limits of 8, 30 and 15 pg mL(-1) and dynamic ranges covering three orders of magnitude.

Polydopamine-functionalization of graphene oxide to enable dual signal amplification for sensitive surface plasmon resonance imaging detection of biomarker.

Surface plasmon resonance imaging (SPRi) is one of the powerful tools for immunoassays with advantages of label-free, real-time, and high-throughput; however, it often suffers from limited sensitivity. Herein we report a dual signal amplification strategy utilizing polydopamine (PDA) functionalization of reduced graphene oxide (PDA-rGO) nanosheets for sensitive SPRi immunoassay in serum. The PDA-rGO nanosheet is synthesized by oxidative polymerization of dopamine in a gentle alkaline solution in the presence of graphene oxide (GO) sheets and then is antibody-conjugated via a spontaneous reaction between the protein and the PDA component. In the dual amplification mode, the first signal comes from capture of the antibody-conjugated PDA-rGO to form sandwiched immunocomplexes on the SPRi chip, followed by a PDA-induced spontaneous gold reductive deposition on PDA-rGO to further enhance the SPRi signal. The detection limit as low as 500 pg mL(-1) is achieved on a nonfouling SPRi chip with high specificity and a wide dynamic range for a model biomarker, carcinoembryonic antigen (CEA) in 10% human serum.

Graphene oxide-enabled tandem signal amplification for sensitive SPRi immunoassay in serum.

A tandem signal amplification using bioconjugated graphene oxide and subsequent silver catalytic deposition for surface plasmon resonance imaging (SPRi) to sensitively and specifically immunoassay tumor biomarkers in serum, achieving a limit of detection down to 100 pg mL(-1) with a broad dynamic range for α-Fetoprotein (AFP) is reported.

Sensitive competitive immunoassay of multiple mycotoxins with non-fouling antigen microarray.

Various mycotoxins with strong carcinogenesis and toxicity are fatal threats in food safety, and require highly sensitive and high-throughput detections greatly. Herein a fluorescent competitive immunoassay microarray based on a non-fouling polymer brush, poly[(ethylene glycol) methacrylate-co-glycidyl methacrylate] (POEGMA-co-GMA) is explored to sensitively detect multiple mycotoxins with aflatoxin B1 (AFB1), ochratoxin A (OTA) and zearalenone (ZEN) as template targets. Due to uniformly large protein loading and high resistance to nonspecific protein absorption of the POEGMA-co-GMA brush, the optimal microarray exhibits wide dynamic ranges of three orders of magnitudes and low detection limits of 4, 4 and 3 pg mL(-1), respectively, which is much better than that obtained with an epoxy-functionalized antigen microarray, and is comparable or even better than the conventional ELISA method. This work offers a powerful high-throughput tool to fast screening of toxins in food quality and environmental monitoring.

HCV subtype characterization among injection drug users: implication for a crucial role of Zhenjiang in HCV transmission in China.

BACKGROUND: HCV transmission is closely associated with drug-trafficking routes in China. However, the transmission route of HCV in Eastern China remains unclear. Here, we investigate the role of Zhenjiang city of Jiangsu province, an important transportation hub linking Shanghai with other regions of China, in HCV transmission. METHODOLOGY/PRINCIPAL FINDINGS: A total of 141 whole blood samples were collected from injection drug users (IDUs) in Zhenjiang and then tested for HCV infection. Of them, 115 HCV positive plasmas were subjected to RNA extraction, RT-PCR amplification, and sequencing. The subtype characterization and the evolutionary origin of HCV strains circulating in Zhenjiang were determined using polygenetic or phylogeographic analyses. Seven HCV subtypes 1b, 2a, 3a, 3b, 6a, 6e and 6n were detected among Zhenjiang IDUs, showing a complex HCV epidemic. The most predominant subtypes were 3a (38%) and 1b (26.8%). Among these subtypes, subtypes 3b, 6n and 6e originated from Southwestern China (i.e., Yunnan and/or Guangxi), subtypes 2a and 6a from Southern China (i.e., Guangdong), subtype 1b from Central (i.e., Henan) and Northwestern (i.e., Xinjiang) China, and subtype 3a from Southwestern (i.e., Yunnan) and Northwestern (i.e., Xinjiang) China. From Zhenjiang, subtypes 1b and 2a were further spread to Eastern (i.e., Shanghai) and Northern (i.e., Beijing) China, respectively. CONCLUSIONS/SIGNIFICANCE: The mixing of seven HCV subtypes in Zhenjiang from all quarters of China indicates that as an important middle station, Zhenjiang plays a crucial role in HCV transmission, just as it is important in population migration between other regions of China and Eastern China.

High Prevalence of Hepatitis C virus Among Injection Drug Users in Zhenjiang, Jiangsu, China.

The constant increase in the number of drug users and rapidly spread of Hepatitis C virus (HCV) and Human immunodeficiency virus (HIV) among drug users result in a serious public health problem in China. To investigate HCV prevalence among drug users in Zhenjiang city, Jiangsu, China, 207 drug users from Zhenjiang were enrolled in this study during 2009 and the prevalence of HCV, HIV and syphilis infection were detected. HCV prevalence among injection drug users (IDUs) was 81.6%, significantly higher than that (22.9%) among oral drug users (P < 0.001), suggesting a strong association of HCV infection with injection drug use (IDU). Most drug users were more than 25 years old (89.2%), single (60.5%, including single and divorced/widowed), and had a history of drug abuse over 6 years (92.9%). HCV prevalence among drug users with middle (72.6%) or high (83.8%) school diplomas was significantly higher than that among those with lower (46.9%) education level (P = 0.007). HCV prevalence among IDUs did not obviously change along with the increase in duration of drug use and in frequency of injection per day, suggesting less association of HCV infection with both variables. These results suggest that most Chinese addicts might start drug use after their middle/high school education. To reduce drug use and to prevent HIV and HCV transmission via IDU, large-scale drug prevention educations should be urgently conducted in all China's middle and high schools.

Near full-length genome characterization of an HIV-1 CRF01_AE strain in Jiangsu, China: evidence of two independent introductions from Fujian.

The occurrence of a novel CRF01_AE-associated recombinant in Jiangsu implies the importance of characterizing full-length CRF01_AE genomic sequence from injecting drug users (IDUs). Here, we reported a near full-length CRF01_AE sequence 07JSWX045 obtained from a Jiangsu IDU, using a modified method. The sequence analyses of 07JSWX045 revealed several interesting findings. First, 07JSWX045 was phylogenetically close to CRF01_AE strains circulating among Jiangsu men who have sex with men (MSM), implying a recent common ancestor. Second, 07JSWX045 was not genetically associated with the CRF01_AE part of the new CRF01_AE/07_BC recombinant found in Jiangsu. Third, both 07JSWX045 and the CRF01_AE parent of CRF01/07 recombinant phylogenetically clustered with two different CRF01_AE subgroups circulating in Fujian, respectively. It suggests that at least two genetically independent CRF01_AE descendants are circulating in Jiangsu possibly via two independent introductions from Fujian. Fourth, two AZT resistance mutations in the RT gene were detected within patient JSWX045, who did not receive any antiviral therapy before sampling, providing valuable bioinformatics sites for investigating the epidemic origin and molecular properties of Jiangsu CRF01_AE strains. Furthermore, patient JSWX045 had two high-risk behaviors including injection drug use and heterosexual contact. He might have been initially infected with CRF01_AE via heterosexual contact, and then introduced this subtype to other people via injection drug use. Therefore, increasing concern is urgently needed for those persons who often have more than two high-risk behaviors.