Gold nanoprisms as a hybrid <Emphasis Type="Italic">in vivo</Emphasis> cancer theranostic platform for <Emphasis Type="Italic">in situ</Emphasis> photoacoustic imaging,angiography, and localized hyperthermia

The development of high-resolution nanosized photoacoustic contrast agents is an exciting yet challenging technological advance. Herein, antibody (breast cancer-associated antigen 1 (Brcaa1) monoclonal antibody)- and peptide (RGD)-functionalized gold nanoprisms (AuNprs) were used as a combinatorial methodology for in situ photoacoustic imaging, angiography, and localized hyperthermia using orthotopic and subcutaneous murine gastric carcinoma models. RGD-conjugated PEGylated AuNprs are available for tumor angiography, and Brcaa1 monoclonal antibody-conjugated PEGylated AuNprs are used for targeting and for in situ imaging of gastric carcinoma in orthotopic tumor models. In situ photoacoustic imaging allowed for anatomical and functional imaging at the tumor site. In vivo tumor angiography imaging showed enhancement of the photoacoustic signal in a time-dependent manner. Furthermore, photoacoustic imaging demonstrated that tumor vessels were clearly damaged after localized hyperthermia. This is the first proof-of-concept using two AuNprs probes as highly sensitive contrasts and therapeutic agents for in situ tumor detection and inhibition. These smart antibody/peptide AuNprs can be used as an efficient nanotheranostic platform for in vivo tumor detection with high sensitivity, as well as for tumor targeting therapy, which, with a single-dose injection, results in tumor size reduction and increases mice survival after localized hyperthermia treatment.

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<Emphasis Type="Italic">In situ</Emphasis> thickness control of black phosphorus field-effect transistors via ozone treatment

A simple and reproducible method to control the thickness of black phosphorus flakes in real time using a UV/ozone treatment is demonstrated. Back-gated black phosphorus field-effect transistors (FETs) were fabricated using thick black phosphorus flakes obtained by thinning of black phosphorus, as oxygen radicals generated by UV irradiation formed phosphorus oxides on the surface. In order to monitor the thickness effect on the electrical properties, the fabricated FETs were loaded in the UV/ozone chamber, where both the optical (micro-Raman spectroscopy and optical microscopy) and electrical properties (current–voltage characteristics) were monitored in situ. We observed an intensity decrease of the Raman modes of black phosphorus while the field-effect mobility and on/off ratio increased by 48% and 6,800%, respectively. The instability in ambient air limits the investigation and implementation of ultra-thin black phosphorus. However, the method reported in this study allowed us to start with thick black phosphorous flakes, providing a reliable approach for optimizing the electrical performance of black phosphorus-based electronic devices. We believe that these results can motivate further studies using mono- and few-layer black phosphorus.

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<Emphasis Type="Italic">In situ</Emphasis> imaging of layer-by-layer sublimation of suspended graphene

An individual suspended graphene sheet was connected to a scanning tunneling microscopy probe inside a transmission electron microscope, and Joule heated to high temperatures. At high temperatures and under electron beam irradiation, the few-layer graphene sheets were removed layer-by-layer in the viewing area until a monolayer graphene was formed. The layer-by-layer peeling was initiated at vacancies in individual graphene layers. The vacancies expanded to form nanometer-sized holes, which then grew along the perimeter and propagated to both the top and bottom layers of a bilayer graphene joined by a bilayer edge. The layer-by-layer peeling was induced by atom sublimation caused by Joule heating and facilitated by atom displacement caused by high-energy electron irradiation, and may be harnessed to control the layer thickness of graphene for device applications.      

Shedding light on electrodeposition dynamics tracked <Emphasis Type="Italic">in situ</Emphasis> via soft X-ray coherent diffraction imaging

The in situ physicochemical analysis of nanostructured functional materials is crucial for advances in their design and production. X-ray coherent diffraction imaging (CDI) methods have recently demonstrated impressive potential for characterizing such materials with a high spatial resolution and elemental sensitivity; however, moving from the current ex situ static regime to the in situ dynamic one remains a challenge. By combining soft X-ray ptychography and single-shot keyhole CDI, we performed the first in situ spatiotemporal study on an electrodeposition process in a sealed wet environment, employed for the fabrication of oxygen-reduction catalysts, which are key components for alkaline fuel cells and metal-air batteries. The results provide the first experimental demonstration of theoretically predicted Turing–Hopf electrochemical pattern formation resulting from morphochemical coupling, adding a new dimension for the in-depth in situ characterization of electrodeposition processes in space and time.

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Multifunctional core/satellite polydopamine@Nd<Superscript>3+</Superscript>-sensitized upconversion nanocomposite: A single 808 nm near-infrared light-triggered theranostic platform for <Emphasis Type="Italic">in vivo</Emphasis> imaging-guided photothermal therapy

Significant attenuation and overheating,caused by the absorption of the excitation band (980 nm) in water,are the major obstacles in the in vivo application of lanthanide-doped upconversion nanopartides (UCNPs).Therefore,appropriately-structured Nd3+-doped UCNPs with 808 nm excitation could be a promising alternative.Herein,we developed core-shell-shell structured Nd3+-sensitized UCNPs as imaging agents,and decorated them onto the surface of polydopamine (PDA) to construct a novel multifunctional core/satellite nanotheranostic (PDA@UCNPs) for in vivo imaging guidance photothermal therapy using single 808 nm laser irradiation.The core-shell-shell structured design enabled outstanding upconversion luminescence properties and strong X-ray attenuation,thereby making the nanocomposites potential candidates for excellent upconversion luminescence/computed tomography dual modal imaging.In addition,the PDA core not only provides high photothermal conversion efficiency and outstanding antitumor effect,but also endows the platform with robust biocompatibility owing to its natural features.Therefore,this multifunctional nanocomposite could be a promising theranostic in future oncotherapy,with high therapeutic effectiveness but low side effects.This study would stimulate interest in designing bioapplication-compatible multifunctional nanocomposites,especially for cancer diagnosis and treatment in vivo.     

Rapid and multimodal <Emphasis Type="Italic">in vivo</Emphasis> bioimaging of cancer cells through <Emphasis Type="Italic">in situ</Emphasis> biosynthesis of Zn&;Fe nanoclusters

Early diagnosis remains highly important for efficient cancer treatment,and hence,there is significant interest in the development of effective imaging strategies.This work reports a new multimodal bioimaging method for accurate and rapid diagnosis of cancer cells by introducing aqueous Fe2+ and Zn2+ ions into cancer cells (i.e.,HeLa,U87,and HepG2 cancer cells).We found that the biocompatible metal ions Fe2+ and Zn2+ forced the cancer cells to spontaneously synthesize fluorescent ZnO nanoclusters and magnetic Fe3O4 nanoclusters.These clusters could then be used for multimodal cancer imaging by combining fluorescence imaging with magnetic resonance imaging and computed tomography imaging.Meanwhile,for normal cells (i.e.,L02) and tissues,neither fluorescence nor any other obvious difference could be detected between preand post-injection.This multimodal bioimaging strategy based on the in situ biosynthesized Zn&Fe oxide nanoclusters might therefore be useful for early cancer diagnosis and therapy.     

<Emphasis Type="Italic">In situ</Emphasis> TEM observation of dissolution and regrowth dynamics of MoO<Subscript>2</Subscript> nanowires under oxygen

Direct observation of the dissolution behavior of nanomaterials could provide fundamental insight to understanding their anisotropic properties and stability.The dissolution mechanism in solution and vacuum has been well documented.However,the gas-involved dissolution and regrowth have seldom been explored and the mechanisms remain elusive.We report herein,an in situ TEM study of the dissolution and regrowth dynamics of MoO2 nanowires under oxygen using environmental transmission electron microscopy (ETEM).For the first time,oscillatory dissolution on the nanowire tip is revealed,and,intriguingly,simultaneous layer-by-layer regrowth on the sidewall facets is observed,leading to a shorter and wider nanowire.Combined with first-principles calculations,we found that electron beam irradiation caused oxygen loss in the tip facets,which resulted in changing the preferential growth facets and drove the morphology reshaping.     

<Emphasis Type="Italic">In situ</Emphasis> polymerization on biomacromolecules for nanomedicines

Biopharmaceuticals, including proteins, DNAs, and RNAs, hold vast promise for the treatment of many disorders, such as cancer, diabetes, autoimmune diseases, infectious diseases, and rare diseases. The application of biopharmaceuticals, however, is limited by their poor stability, immunogenicity, suboptimal pharmacokinetic performance, undesired tissue distribution, and low penetration through biological barriers. In situ polymerization provides an appealing and promising platform to improve the pharmacological characteristics of biopharmaceuticals. Instead of the traditional “grafting to” polymer–biomolecule conjugation, in situ polymerization grows polymers on the surfaces of the biomacromolecules, resulting in easier purification procedures, high conjugation yields, and unique structures. Herein, this review surveys recent advances in the polymerization methodologies. Additionally, we further review improved therapeutic performance of the resultant nanomedicines. Finally, the opportunities, as well as the challenges, of these nanocomposites in the biomedical fields are discussed.     

<Emphasis Type="Italic">In situ</Emphasis> atomic-scale analysis of Rayleigh instability in ultrathin gold nanowires

Comprehensive understanding of the structural/morphology stability of ultrathin (diameter < 10 nm) gold nanowires under real service conditions (such as under Joule heating) is a prerequisite for the reliable implementation of these emerging building blocks into functional nanoelectronics and mechatronics systems. Here, by using the in situ transmission electron microscopy (TEM) technique, we discovered that the Rayleigh instability phenomenon exists in ultrathin gold nanowires upon moderate heating. Through the controlled electron beam irradiation-induced heating mechanism (with < 100 °C temperature rise), we further quantified the effect of electron beam intensity and its dependence on Rayleigh instability in altering the geometry and morphology of the ultrathin gold nanowires. Moreover, in situ high-resolution TEM (HRTEM) observations revealed surface atomic diffusion process to be the dominating mechanism for the morphology evolution processes. Our results, with unprecedented details on the atomic-scale picture of Rayleigh instability and its underlying physics, provide critical insights on the thermal/structural stability of gold nanostructures down to a sub-10 nm level, which may pave the way for their interconnect applications in future ultralarge- scale integrated circuits.

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Electrochemical and <Emphasis Type="Italic">in situ</Emphasis> spectroelectrochemical studies of gold nanoparticles immobilized Nafion matrix modified electrode

Electrochemical and in situ spectroelectrochemical behaviours of phenosafranine (PS⁺) were studied at the gold nanoparticles (Au_Nps) immobilized Nafion (Nf) film coated glassy carbon (GC) and indium tin oxide (ITO) electrodes. Cyclic voltammetric studies showed that the PS⁺ molecules strongly interact with the Au_Nps immobilized in the Nf matrix through the electrostatic interaction. The presence of Au_Nps in the Nf film improved the electrochemical characteristics of the incorporated dye molecules. The emission spectra of Nf-Au_Nps-PS⁺ films showed that the incorporated PS⁺ was quenched by Au_Nps and it could be explained based on the electronic interaction between the Au_Nps and PS⁺ molecules. The in situ spectroelectrochemical study showed an improved electrochemical characteristic of the incorporated PS⁺ molecules at the ITO/Nf-Au_Nps electrode when compared to the ITO/Nf electrode.     

Highly efficient gene silencing and bioimaging based on fluorescent carbon dots <Emphasis Type="Italic">in vitro</Emphasis> and <Emphasis Type="Italic">in vivo</Emphasis>

Small interfering RNA (siRNA) is an attractive therapeutic candidate for sequencespecific gene silencing to treat incurable diseases using small molecule drugs.However,its efficient intracellular delivery has remained a challenge.Here,we have developed a highly biocompatible fluorescent carbon dot (CD),and demonstrate a functional siRNA delivery system that induces efficient gene knockdown in vitro and in vivo.We found that CD nanoparticles (NPs) enhance the cellular uptake of siRNA,via endocytosis in tumor cells,with low cytotoxicity and unexpected immune responses.Real-time study of fluorescence imaging in live cells shows that CD NPs favorably localize in cytoplasm and successfully release siRNA within 12 h.Moreover,we demonstrate that CD NP-mediated siRNA delivery significantly silences green fluorescence protein (GFP) expression and inhibits tumor growth in a breast cancer cell xenograft mouse model of tumor-specific therapy.We have developed a multi functional siRNA delivery vehicle enabling simultaneous bioimaging and efficient downregulation of gene expression,that shows excellent potential for gene therapy.     

Thermally removable <Emphasis Type="Italic">in-situ</Emphasis> formed ZnO template for synthesis of hierarchically porous N-doped carbon nanofibers for enhanced electrocatalysis

Rational design and simple synthesis of one-dimensional nanofibers with high specific surface areas and hierarchically porous structures are still challenging.In the present work,a novel strategy utilizing a thermally removable template was developed to synthesize hierarchically porous N-doped carbon nanofibers (HP-NCNFs) through the use of simple electrospinning technology coupled with subsequent pyrolysis.During the pyrolysis process,ZnO nanoparticles can be formed in situ and act as a thermally removable template due to their decomposition and sublimation under high-temperature conditions.The resulting HP-NCNFs have lengths of up to hundreds of micrometers with an average diameter of 300 nm and possess a hierarchically porous structure throughout.Such unique structures endow HP-NCNFs with a high specific surface area of up to 829.5 m2·g-1,which is 2.6 times higher than that (323.2 m2·g-1) of conventional N-doped carbon nanofibers (NCNFs).Compared with conventional NCNFs,the HP-NCNF catalyst exhibited greatly enhanced catalytic performance and improved kinetics for the oxygen reduction reaction (ORR) in alkaline media.Moreover,the HP-NCNFs even showed better stability and stronger methanol crossover effect tolerance than the commercial Pt-C catalyst.The optimized ORR performance can be attributed to the synergetic contribution of continuous and three-dimensional (3D) cross-linked structures,graphene-like structure on the edge of the HPNCNFs,high specific surface area,and a hierarchically porous structure.     

<Emphasis Type="Italic">In situ</Emphasis> etching for total control over axial and radial nanowire growth

We report a method using in situ etching to decouple the axial from the radial nanowire growth pathway, independent of other growth parameters. Thereby a wide range of growth parameters can be explored to improve the nanowire properties without concern of tapering or excess structural defects formed during radial growth. We demonstrate the method using etching by HCl during InP nanowire growth. The improved crystal quality of etched nanowires is indicated by strongly enhanced photoluminescence as compared to reference nanowires obtained without etching.      

<Emphasis Type="Italic">In vivo</Emphasis> evaluation of riboflavin receptor targeted fluorescent USPIO in mice with prostate cancer xenografts

Riboflavin (Rf) receptors bind and translocate Rf and its phosphorylated forms (e.g. flavin mononucleotide, FMN) into cells where they mediate various cellular metabolic pathways. Previously, we showed that FMN-coated ultrasmall superparamagnetic iron oxide (FLUSPIO) nanoparticles are suitable for labeling metabolically active cancer and endothelial cells in vitro. In this study, we focused on the in vivo application of FLUSPIO using prostate cancer xenografts. Size, charge, and chemical composition of FLUSPIO were evaluated. We explored the in vitro specificity of FLUSPIO for its cellular receptors using magnetic resonance imaging (MRI) and Prussian blue staining. Competitive binding experiments were performed in vivo by injecting free FMN in excess. Bio-distribution of FLUSPIO was determined by estimating iron content in organs and tumors using a colorimetric assay. AFM analysis and zeta potential measurements revealed a particulate morphology approximately 20–40 nm in size and a negative zeta potential (–24.23 ± 0.15 mV) in water. X-ray photoelectron spectroscopy and time-of-flight secondary ion mass spectrometry data confirmed FMN present on the USPIO nanoparticle surface. FLUSPIO uptake in prostate cancer cells and human umbilical vein endothelial cells was significantly higher than that of control USPIO, while addition of excess of free FMN reduced accumulation. Similarly, in vivo MRI and histology showed specific FLUSPIO uptake by prostate cancer cells, tumor endothelial cells, and tumor-associated macrophages. Besides prominent tumor accumulation, FLUSPIO accumulated in the liver, spleen, lung, and skin. Hence, our data strengthen our hypothesis that targeting riboflavin receptors is an efficient approach to accumulate nanomedicines in tumors opening perspectives for the development of diagnostic and therapeutic systems.     

Green synthesis of zinc oxide nanoparticles using <Emphasis Type="Italic">Citrus sinensis</Emphasis> extract

This work addresses a low cost, non-toxic green synthesis of zinc oxide nanoparticles prepared using different amounts of Citrus sinensis extract. The zinc oxide nanoparticles presented the Zn–O bond at 618 cm^?1, a crystalline growth in a purely hexagonal wurtzite crystal structure, and different size and shape homogeneity depending on the amount of extract used. The band gap of the ZnO was at around 2.91 eV for all samples. The photocatalytic degradation studies were carried out using methylene blue with the zinc oxide nanoparticles under UV light; where sample M2 presented a degradation of around 83% at 120 min. These results presented a better degradation rate than commercially available zinc oxide nanoparticles.     

Preparation and characterization of antibacterial graphene oxide functionalized with polymeric <Emphasis Type="Italic">N</Emphasis>-halamine

Organic–inorganic composites have also gained much attention owing to their excellent combined properties. For the enhancement of the bacteria-inactivation ability of graphene oxide (GO), poly[5,5-dimethyl-3-(3′-triethoxysilylpropyl)hydantoin] (PSPH) was synthesized and attached onto GO through covalent bond. The synthesized inorganic–organic composites (GO-PSPH) were characterized by FT-IR, XPS, XRD, AFM, SEM, etc. After chlorination treatment by sodium hypochlorite, biocidal efficacies of the chlorinated GO-PSPH (GO-PSPH-Cl) against S. aureus (ATCC 6538) and E. coli O157:H7 (ATCC 43895) were tested. The antibacterial testing results showed that the GO-PSPH-Cl has great antibacterial activity and could completely inactivate 5.5 × 10⁶ CFU/mL of S. aureus and 1.2 × 10⁸ CFU/mL of E. coli O157:H7 within 30 and 10 min of contact time, respectively.     

Design of active and stable oxygen reduction reaction catalysts by embedding Co<Subscript><Emphasis Type="Italic">x</Emphasis></Subscript>O<Subscript><Emphasis Type="Italic">y</Emphasis></Subscript> nanoparticles into nitrogen-doped carbon

The oxygen reduction reaction (ORR) is essential in research pertaining to life science and energy. In applications, platinum-based catalysts give ideal reactivity, but, in practice, are often subject to high costs and poor stability. Some cost-efficient transition metal oxides have exhibited excellent ORR reactivity, but the stability and durability of such alternative catalyst materials pose serious challenges. Here, we present a facile method to fabricate uniform Co _x O _y nanoparticles and embed them into N-doped carbon, which results in a composite of extraordinary stability and durability, while maintaining its high reactivity. The half-wave potential shows a negative shift of only 21 mV after 10,000 cycles, only one third of that observed for Pt/C (63 mV). Furthermore, after 100,000 s testing at a constant potential, the current decreases by only 17%, significantly less than for Pt/C (35%). The exceptional stability and durability results from the system architecture, which comprises a thin carbon shell that prevents agglomeration of the Co _x O _y nanoparticles and their detaching from the substrate.

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<Emphasis Type="Italic">In situ</Emphasis> anchor of magnetic Fe<Subscript>3</Subscript>O<Subscript>4</Subscript> nanoparticles onto natural maifanite as efficient heterogeneous Fenton-like catalyst

In situ anchor of magnetic Fe₃O₄ nanoparticles (NPs) onto the surface of natural maifanite was realized by chemical oxidation coprecipitation in hot alkaline solution. The Fe₃O₄/maifanite composites were characterized by XRD, FTIR, SEM, and TEM. These results indicated that polycrystalline Fe₃O₄ NPs with inverse spinel structure were formed and tightly dispersed on maifanite surface. Based on the measurement of surface Zeta potential of maifanite at different medium pHs, the possible combination mechanism between natural maifanite and Fe₃O₄ NPs was proposed. Then, the asobtained composites were developed as highly efficient heterogeneous Fenton-like catalyst for the discoloration of an azo dye, Methyl Orange (MO). The comparative tests on MO discoloration in different systems revealed that Fe₃O₄/maifanite composite exhibited much higher Fenton-like catalytic activity than Fe₃O₄ NPs and the heterogeneous Fentonlike reaction governed the discoloration of MO. Kinetic results clearly showed that MO discoloration process followed the second-order kinetic model. Fe₃O₄/maifanite composites exhibited the typical ferromagnetic property detected by VSM and could be easily separated from solution by an external magnetic field.     

Preclinical evaluation of <Superscript>99<Emphasis Type="Italic">m</Emphasis> </Superscript>Tc-histidine as a possible tumor imaging agent

Radiolabeling of histidine (Hist), an essential amino acid, with ^99mTc was performed. The radiochemical yield higher than 95% was achieved with stannous chloride as a reducing agent. Factors affecting the radiochemical yield (histidine amount, stannous chloride amount, reaction time, pH of the reaction mixture) were studied in detail, and the reaction conditions were optimized. In vitro stability of the radiolabeled complex was checked, and it was found to be stable for up to 6 h. ^99mTc-Hist was injected intravenously into normal and tumor-bearing mice. Biodistribution studies revealed that the ^99mTc-Hist uptake in tumor sites was 10 and 16% ID/g in ascites and 7 and 9.2% ID/g in thigh solid tumor at 60 and 120 min post injection, respectively. The amount of ^99mTc-Hist in ascites and solid tumor increased with time and then decreased slowly. Thus, ^99mTc-Hist can be used as a potential agent for imaging tumor sites.     

<Emphasis Type="Italic">Aloe vera</Emphasis> (L.) Burm.f. extract reduced graphene oxide for supercapacitor application

An eco-friendly and effective reducing agent to convert Graphene Oxide (GO) to reduced Graphene Oxide (rGO) is reported. The oxygen scavenging property of Aloe vera (L.) Burm.f. (AV) extract is successfully utilized to remove oxygen functionalities on GO. The synthesized reduced Graphene oxide (ARGO) is analyzed using UV–Visible spectroscopy, Raman spectroscopy and FT-IR analysis. Complete GO reduction is achieved within 3 h with 30 mM AV extract and is confirmed by the XRD results. The high resolution transmission electron microscopy images provide clear evidence for the formation of single layer of graphene (rGO). The mechanism of reduction of GO by the AV extract is proposed. The rGO shows good charge storage properties with stable cycling up to 1000 cycles, demonstrated by the electrochemical method. The findings suggest that the Aloe vera (L.) Burm.f. (AV) extract reduced graphene oxide was found to be suitable for supercapacitor applications.