Nanoscale & Nanoscale Advances Blog

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

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

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

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.

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.

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.

Reversible engineering of the pore size and philicity of mesoporous SBA via dynamic covalent chemistry triggered by changes in pH.

Control of surface chemistry is important for utilisation of mesoporous silicas in many applications such as catalysis, drug delivery and separation sciences. Due to the mostly irreversible nature of covalent functionalisations and lack of rigidity in supramolecular approaches, in this study, dynamic covalent chemistry was used to reversibly alter the chemical coating on the surface of amine functional mesoporous silica SBA-15. This was achieved through the condensation reaction of the primary amine on SBA-15 with 4-decyloxybenzaldehyde (4-DB) to form an imine containing a hydrophobic decyl chain. This step both reduced the pore size and hydrophilicity of the pore surface, however, could be reversed by cleaving the imine at low pH in an ethanol/water mixture.

Dynamic control of the pore properties was demonstrated using the catalytic reduction of p-nitrophenol in aqueous conditions by gold nanoparticles, which were imbedded into both amine and imine/decyl SBA-15 materials. The more porous/hydrophilic amine-based material completely reduced p-nitrophenol to p-aminophenol after 30 minutes, whereas the more hydrophobic imine-based surface exhibited no catalytic activity. The authors suggest that this methodology could be used to generate a host of new covalently functionalised materials with tuneable surface properties.

Reversible control of pore size and surface chemistry of mesoporous silica through dynamic covalent chemistry: philicity mediated catalysis
Dheeraj Kumar Singh, B. V. V. S. Pavan Kumar and M. Eswaramoorthy
Nanoscale, 2015, Advance Article. DOI: 10.1039/C5NR02959G

Dr Mike Barrow is a guest web writer for the Nanoscale blog. He currently works as a Postdoctoral Researcher at the University of Liverpool.