Archive for the ‘Hot Article’ Category

Direct real-time detection of single proteins using silicon nanowire-based electrical circuits

The development of analytical devices that convert biological response into an electrical signal is a very important goal with great potential benefits for clinical diagnostics, environmental science, and defense.

In a recent communication published in Nanoscale, researchers discuss findings from a newly developed single silicon nanowire (SiNW) based biosensor, which is able to directly detect protein adsorption/desorption at single-molecule resolutions.

Fig. 1 Schematic demonstration of SiNW FET-based electrical biosensors, where Au electrodes are passivated by using a thermally deposited 50 nm-thick SiO2 layer. The inset shows how His-tag F1-ATPase is immobilized on the surface of SiNWs through Ni2+ chelation.

SiNW’s were synthesised following an Au-catalysed vapor deposition method and then high-density SiNW array devices were fabricated on silicon substrates using photolithography. Subsequently the devices were functionalized in a stepwise manner to impart the biomolecule recognizing Nickel functionality, and characterized with XPS and FTIR spectroscopy.

By combining theses devices with microfluidic systems, the authors were able to achieve real-time, direct detection of the chelation between Nickel and the imidazole of His-tags in the target biomolecules (F1 ATPases) at the single-event level. This nondestructive and label-free sensor shows great promise for number verification and real-time monitoring of proteins in complex biological systems.

Direct real-time detection of single proteins using silicon nanowire-based electrical circuits
Jie Li, Gen He, Hiroshi Ueno, Chuancheng Jia, Hiroyuki Noji, Chuanmin Qi and Xuefeng Guo
Nanoscale, 2016, DOI: 10.1039/C6NR04103E

Alexander Cook is a guest web writer for the RSC journal blogs. He is a PhD researcher in the Perrier group at the University of Warwick, focusing on polymer materials and their use in various applications. Follow him on twitter @alexcook222

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HOT article: Ultra-small lipid–polymer hybrid nanoparticles for tumor-penetrating drug delivery

When it comes to cancer treatment, smaller can sometimes be better, as a new HOT article published in Nanoscale has shown. New ultra-small hybrid nanoparticles, developed by Jiangfang Zhang and a team based at the University of California, have proven highly effective at delivering anti-cancer drugs in mice – the nanoparticles, which are under 25nm in size, could penetrate deep into the tumours of the mice to release the drug where it would be most effective.

The size of drug delivery nanocarriers has a crucial role in how effective they are at moving through the body: too large, and they will be cleared by the liver; too small, and they will be filtered by the kidneys. Cancer drug carriers work best at sizes below 50nm, where they can more easily infiltrate tumours, but preventing such small particles from aggregating once synthesised can be a challenge. Zhang’s team used both lipids and polymers to make their nanoparticles highly stable, even in physiological conditions –  the polymer cores took up the hydrophobic drug, while the lipid coating provided stability and protection from the aqueous environment of the body.

The nanoparticles were targeted to tumour cells by conjugating them to folate ligands – when injected into mice with induced tumours, the number of target nanoparticles present within the tumours was three times that of non-targeted carriers. What’s more, the anti-cancer drug docetaxel could be loaded into the nanoparticles and used to treat the mice, with highly promising results. Over half of the mice treated with the hybrid nanocarriers were still alive 64 days after having tumours induced, a significant extension compared to a clinically used drug treatment.

Read the full article here:

Ultra-small lipid–polymer hybrid nanoparticles for tumor-penetrating drug delivery

Diana Dehaini, Ronnie H. Fang, Brian T. Luk, Zhiqing Pang, Che-Ming J. Hu, Ashley V. Kroll, Chun Lai Yu,  Weiwei Gao and Liangfang Zhang*
Nanoscale, 2016, Advance Article

Susannah May is a guest web writer for the RSC Journal blogsShe currently works in the Publishing Department of the Royal Society of Chemistry, and has a keen interest in biology and biomedicine, and the frontiers of their intersection with chemistry. She can be found on Twitter using @SusannahCIMay.

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iPAINT: brushing-up on super resolution microscopy

In recent years, super-resolution microscopy has enabled researchers to explore biological interfaces at the nanoscale. Single-molecule localization methods, such as point accumulation for imaging in nanoscale topography (PAINT), are fundamental techniques for studying the morphology and architecture of living matter. While super-resolution microscopy techniques like PAINT have acquired the interest of researchers in biology, it remains elusive to applications in soft matter and materials science.

In issue 16 of Nanoscale, researchers from the Netherlands have endeavoured to overcome the limitations of PAINT, such as a pre-requisite for hydrophobic domains or specific ligand/receptor pairs, by introducing interface point accumulation for imaging in nanoscale topography (iPAINT). In short, this new technique enables nanometre resolution imaging of interfaces by non-covalent, continuous labelling during imaging. This was achieved by labelling silica nanoparticles with polyethylene glycol (PEG) end-functionalized with a photoactivatable rhodamine analogue (PEG552) that is able to continuously adsorb and desorb from the interface. This method of labelling is essential for interfaces such as emulsions, foams and crystals like ice.

By employing iPAINT as a generic imaging method, the authors are able to obtain super-solution images at different interfaces in 3D. This innovation allows users to develop PAINT in other fields, such as colloid and interface science, food science, soft matter physics and nanotechnology.

iPAINT: a general approach tailored to image the topology of interfaces with nanometer resolution
A. Aloi, N. Vilanova, L. Albertazzi and I. K. Voets
Nanoscale, 2016, DOI: 10.1039/C6NR00445H

Dr Lee Barrett is a guest web writer for the Nanoscale blog. Lee is currently a postdoctoral researcher in the Centre for Molecular Nanometrology at the University of Strathclyde. His research is currently focused on the development of nanoparticle-based sensors and surface enhanced Raman scattering (SERS). Follow him on twitter @L_Bargie

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HOT article: Ionizing radiation improves glioma-specific targeting of superparamagnetic iron oxide nanoparticles conjugated with cmHsp70.1 monoclonal antibodies (SPION–cmHsp70.1)

In this HOT article, tumour-specific targeting using superparamagnetic iron oxide nanoparticles (SPIONs) combined with ionising radiation is investigated. Heat shock protein Hsp70 is known to be expressed by cells exposed to stressful conditions or specifically on the membrane of highly aggressive tumour cells.  SPIONs, which are negative contrast agents for magnetic resonance imaging (MRI), were synthesised to contain the Hsp70 specific antibody (cmHsp70.1) to increase uptake into various tumour cells.

Conjugation of the cmHsp70.1 was accomplished by introducing amine groups to the dextran polymer coating of SPIONs, allowing covalent attachment to the carboxylic acid functional groups of the antibody through carbodiimide coupling. This was shown to dramatically increase loading of iron oxide into various tumour cells, compared to unconjugated SPIONs. By exposing cells to a non-lethal dose of ionising radiation, additional uptake could be achieved as cells express more of the heat shock mHsp70.

The differences in uptake can be seen in the figure below in both in vivo and in vitro environments using MRI and fluorescence microscopy, respectively. This approach has the potential to be clinically relevant for both diagnosis and therapy of tumours.

Figure 1 Targeting of the orthotopic C6 glioma by SPION–cmHsp70.1 conjugates. (A) Magnetic resonance images for the control, non-irradiated animals treated with SPIONs, SPION–cmHsp70.1 particles and irradiated rats (10 Gy) treated with SPION–cmHsp70.1. Images were obtained in RARE-T1, TurboRARE-T2 and FLASH regimens. Retention of the nanoparticles in the tumor presented as hypotensive zones on T2-weighted and gradient echo images (red arrows). (B) Immunofluorescent images of the brain tumor stained with anti-Hsp70 antibodies (green). Nuclei stained with DAPI (blue). Nanoparticles detected using reflective laser scanning at 488 nm (red). Scale bar, 40 μm.

Ionizing radiation improves glioma-specific targeting of superparamagnetic iron oxide nanoparticles conjugated with cmHsp70.1 monoclonal antibodies (SPION–cmHsp70.1)
Maxim A. Shevtsov, Boris P. Nikolaev, Vyacheslav A. Ryzhov, Ludmila Y. Yakovleva, Yaroslav Y. Marchenko, Marina A. Parr, Valerij I. Rolich, Anastasiya L. Mikhrina, Anatolii V. Dobrodumov, Emil Pitkin and Gabriele Multhoff
Nanoscale, 2015,7, 20652-20664, DOI: 10.1039/C5NR06521F, Paper

Dr Mike Barrow is a guest web writer for the Nanoscale blog, he currently works as a Postdoctoral Researcher at the University of Liverpool. Twitter: @mikesyb

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HOT article: Responsive polymer brushes for controlled nanoparticle exposure

In this article, Scheutjens-Fleer self-consistent field (SF-SCF) theory simulations were used to accurately predict the position of a nanoparticle attached to the end-group of a responsive polymer chain surrounded by a majority of non-responsive polymer chains in a mixed brush system.

Certain stimuli such as pH or temperature can be used to create a defined ‘on-off’ switch between a protected ‘off’ state, where the responsive polymer chain is contracted thus burying the nanoparticles well within the non-responsive components, or an ‘on’ state where the nanoparticle is exposed to the medium through swelling of the responsive polymer chains.

The solvent quality was parameterised by the Flory-Huggins interaction parameter (χ) and for nearly all investigated systems there was a sharp transition at the so-called critical χ value between the on-off state.   Design variables for mixed polymer brushes such as grafting density, chain length and nanoparticle size were investigated and all had an effect on the critical χ value, with a larger particle size and grafting density leading to an increase in χ. Fixing the polymer chain length for both responsive and non-responsive polymer chains led to the most optimal switching.

The authors are planning to develop materials from these findings and use the mixed polymer brush-nanoparticle systems as rapidly responsive (bio)sensors with single molecule sensitivity.

Responsive polymer brushes for controlled nanoparticle exposure
Namik Akkilic, Frans A. M. Leermakers and Wiebe M. de Vos
Nanoscale, 2015,7, 17871-17878, DOI: 10.1039/C5NR05150A

Dr Mike Barrow is a guest web writer for the Nanoscale blog, he currently works as a Postdoctoral Researcher at the University of Liverpool. Twitter: @mikesyb

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Micro meets nano: Multicolour gold nanoprobes detect micoRNA biomarkers in serum

Researchers from Chinese Academy of Sciences have investigated the use of molecular beacons (MBs) for the simultaneous detection of multiple microRNA (miRNA) biomarkers.

The MBs were immobilized onto gold nanoparticles (AuNPs) via poly-adenine (poly-A) spacer. In addition, the authors used short oligonucleotides (oligos) consisting of 5 As in order to fill the gaps between MBs on the AuNP surface to ensure stability in salt solutions and obtain greater fluorescence signals.

MBs with 3 different fluorophores were employed in order to enable multiplexed detection of miRNAs in simulated serum samples. The authors reported that each MB specifically bound to its corresponding miRNA target in the presence of 10% fetal bovine serum (FBS), thereby demonstrating the applicability of this method for real biological sample detection.

In recent years, miRNA has emerged as a potential biomarker for many types of diseases, such as cancer, neurological disorders and cardiovascular disease. The need for rapid and sensitive assays for miRNA detection is therefore of great interest. Wang et al. have demonstrated a step in this direction with the research presented here.

Elaborately designed diblock nanoprobes for simultaneous multicolor detection of microRNAs
Chenguang Wang, Huan Zhang, Dongdong Zeng, Wenliang Sun, Honglu Zhang, Ali Aldalbahi, Yunsheng Wang, Lili San, Chunhai Fan, Xiaolei Zuo and Xianqiang Mi
Nanoscale, 2015,7, 15822-15829, DOI: 10.1039/C5NR04618A

Dr Lee Barrett is a guest web writer for the Nanoscale blog. Lee is currently a postdoctoral researcher in the Centre for Molecular Nanometrology at the University of Strathclyde. His research is currently focused on the development of nanoparticle-based sensors and surface enhanced Raman scattering (SERS). Follow him on twitter @L_Bargie

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HOT article: Microgel coating of magnetic nanoparticles via bienzyme mediated free-radical polymerization for colorimetric detection of glucose

Researchers from Qigang Wang’s group have developed a new strategy for the fabrication of core shell magnetic microgels for glucose detection, which is one of the most frequently used tests in clinical environments. Magnetic nanoparticles containing carboxylic acid groups on the surface were used as a starting material to covalently bind the enzyme glucose oxidase (GOx). A second enzyme, horseradish peroxidase, was also attached through a bifunctional polyethylene glycol polymer which ensured a working distance between the two immobilised enzymes. The microgels could be formed by adding glucose and acetylacetone (ACAC) with PEGMA and crosslinker PEGDA. One of the by-products of glucose oxidation, hydrogen peroxide, reacts with ACAC to form radicals that polymerise the monomers resulting in a gel-like coating formed around the enzyme containing particles.

The preparation of the magnetic core–shell microgels.

After polymerisation the enzymes retained their reactivity. Even after 7 days storage, 96% catalytic activity was observed with respect to a fresh sample. The high selectivity towards glucose was demonstrated with other sugars e.g. fructose, lactose and maltose. It is thought that this strategy could be extended to the detection of other biomolecules through new oxidase-HRP systems, as well as being easily translatable to clinical fields.

Microgel coating of magnetic nanoparticles via bienzyme-mediated free-radical polymerization for colorimetric detection of glucose
Qing Wu, Xia Wang, Chuanan Liao, Qingcong Wei and Qigang Wang
Nanoscale, 2015,7, 16578-16582. DOI: 10.1039/C5NR05716G

Dr Mike Barrow is a guest web writer for the Nanoscale blog, he currently works as a Postdoctoral Researcher at the University of Liverpool. Twitter: @mikesyb

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Hybrid nanoparticles: The fight against breast cancer heats up

Gold nanorods with cisplatin-polypeptide wrapping were developed for combinational photothermal therapy and chemotherapy of triple negative breast cancer.

Researchers from China have advanced the fight against breast cancer (BC) by developing a method that targets triple negative breast cancer (TNBC) – a highly aggressive subtype of BC and a form that is challenging to completely eradicate.

Their method consisted of the formation of gold nanorods (GNRs) with a cisplatin-polypeptide wrapping and folic acid (FA) functionalization (FA-GNR@Pt) for the simultaneous targeted photothermal therapy and chemotherapy. These hybrid nanoparticles combine the photothermal conversion properties of GNRs, superior biocompatibility of polypeptide poly(L-glutamic acid) (PGA), chemotoxicity of cisplatin and the tumour targeting ability of FA.  FA-GNR@Pt nanoparticles exhibited temperature increases both in vitro and in vivo using 655 nm NIR laser irradiation and, in combination with systemic administration in mice, were able to inhibit the proliferation and lung metastisis of the 4T1 breast tumour.

The research presented here takes significant steps in furthering the understanding of breast cancer, particularly TNBC, which have increased risk of metastisis.

Near infrared light-actuated gold nanorods with cisplatin–polypeptide wrapping for targeted therapy of triple negative breast cancer
Bing Feng, Zhiai Xu, Fangyuan Zhou, Haijun Yu, Qianqian Sun, Dangge Wang, Zhaohui Tang, Haiyang Yu, Qi Yin, Zhiwen Zhang and Yaping Li
Nanoscale, 2015, 7, 14854-14864.  DOI: 10.1039/C5NR03693C

Dr Lee Barrett is a guest web writer for the Nanoscale blog. Lee is currently a postdoctoral researcher in the Centre for Molecular Nanometrology at the University of Strathclyde. His research is currently focused on the development of nanoparticle-based sensors and surface enhanced Raman scattering (SERS). Follow him on twitter @L_Bargie.

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HOT article: Nanostructured conducting polymer hydrogels for energy storage applications

Future energy storage solutions require a combination of high energy density, high reliability and low manufacturing cost. Conducting polymer hydrogels (CPHs) have emerged in recent years as a viable alternative for energy storage applications, as a Feature article by Shi et al. reports.

CPHs exhibit highly advantageous properties such as a large surface area, tunable mechanical properties and high conductivity compared to other polymers. These materials combine a conductive π–conjugated backbone with a porous structure.

Two synthesis routes are presented: template-guided synthesis (e.g. polymerization of monomers in a non-conductive hydrogel matrix) and direct formation using phytic acid as a gelator and dopant of the polymer.

Independent of synthesis route, CPHs were successfully demonstrated as bulk materials for electrochemical capacitors (also termed “supercaps”), as well as functional binders within Li-ion batteries. By careful modification of the polymer properties, a stable material able to withstand over 10000 charge-discharge cycles was demonstrated. Finally, the current hurdles for mass-market adoption, such as limited mechanical strength, lower conductivity than currently utilized material combinations and a lower capacity are explained, and paths to overcome these are discussed.

Nanostructured conducting polymer hydrogels for energy storage applications
Ye Shi, Lele Peng and Guihua Yu
Nanoscale, 2015, 7, 12796-12806. DOI: 10.1039/C5NR03403E

Sebastian Axmann is a guest web-writer for the Nanoscale blog. His interests comprise manufacturing and metrology of nanostructures as well as their usage in current semiconductor devices. He also posts links to interesting research articles on Twitter: @SebastianAxmann.

Nanoscale, 2015,7, 12796-12806
DOI: 10.1039/C5NR03403E

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HOT article: Bridging the transport pathway of charge carriers in a Ta3N5 nanotube array photoanode for solar water splitting

Besides the wide field of photovoltaics research, additional technologies, such as the direct conversion of H2 via solar water splitting, are currently being researched. A recent article by Zhang et al. presents their findings on improved manufacturing routes for these cells.

For the time being, Ta3N5 is the material of choice as the band gap and structure are both well suited for light absorption. To form a large interfacial area for efficient light conversion within the cells, arrays of hollow nanorods are employed. As the authors describe in their article, earlier attempts of a one-step synthesis route, also evaluated by other researchers, led to weak adhesion of the brittle nanorod film on the substrate. Their new approach utilizes a two-step synthesis route: first, a nanorod layer of Ta2O5 is formed via anodization in a solution with a lower HF concentration compared to that employed by other groups. Next, this weakly adhering layer is removed by sonication and a second layer is formed. The formation of the second layer also employs a low reaction temperature to limit the reaction rate. Finally, this second nanorod layer is nitridated, forming Ta3N5 from the Ta2O5 layer.

(a) Schematic illustration of the synthetic process, (b) top-view SEM image and (c) cross-sectional SEM image of Ta3N5 NTAs.

The resulting layer was found to adhere well on the substrate surface and to exhibit only a few cracks. By further optimization of processing times and the additive material used during nitridation, a maximum current density of 11 mA/cm² at 1.6 V was demonstrated by the authors.

Bridging the transport pathway of charge carriers in a Ta3N5 nanotube array photoanode for solar water splitting
Peng Zhang, Tuo Wang, Jijie Zhang, Xiaoxia Chang and Jinlong Gong
Nanoscale, 2015, Advance Article. DOI: 10.1039/C5NR03013G

Sebastian Axmann is a guest web-writer for the Nanoscale blog. His interests comprise manufacturing and metrology of nanostructures as well as their usage in current semiconductor devices. He also posts links to interesting research articles on Twitter: @SebastianAxmann.

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