Major society chemistry publishers jointly commit to integration with ORCID

ORCID provides an identifier for individuals to use with their name as they engage in research, scholarship and innovation activities, ensuring authors gain full credit for their work.

Today, we signed their open letter, along with ACS Publications, committing to unambiguous identification of all authors that publish in our journals.

The official press release can be read here.

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Serving up anti-cancer cocktails: design, synthesis and evaluation of hybrid inhibitors

Scientists in the area of cancer drug development constantly find ways to target cancer’s Achilles heel. Bcr-Abl is a protein expressed in 95% of all Chronic Myelogenous Leukemia (a type of blood cancer) cases. It remains activated (i.e. switched ON) and instructs cancer cells to divide indefinitely. Bcr-Abl has remained an attractive target for therapy. Yet another attractive therapeutic target is Histone Deacetylase 1 (HDAC1) – a protein known to control cell survival via its ability to influence the turning on and turning off of certain genes.

Previous studies show that the drugs Dasatinib and MS-275 efficiently inhibit the cancer promoting activities of Bcr-Abl and HDAC1 respectively.  Clinical trials also suggest that these drugs, when used independently in separate studies, can be used to treat a variety of solid as well as blood-borne cancers. Bcr-Abl and HDAC1 are components of distinct cellular wiring systems, referred to as signalling pathways, which sustain cell survival and division. Single agent drugs, or drugs that stifle a single cancer-promoting pathway, weed out most cancer cells but also set the stage for drug-resistant cells. Reports suggest that both Dasatinib and MS-275 are associated with cancer drug resistance.

Multi-target inhibitors are a new and evolving class of cancer drugs that can simultaneously inhibit at least two signalling pathways. These compounds  have emerged as a potential solution in circumventing cancer drug resistance. Chen and colleagues at the Department of Organic Chemistry, School of Science, China Pharmaceutical University, China, designed and produced a series of hybrid drug molecules which combine the attributes of the HDAC inhibitor MS-275 with the Bcr-Abl inhibitor Dasatinib.

To determine the effect of the hybrid drugs on cancer cell survival, the research team tested the drug’s ability to halt the growth of three cell types exhibiting features of leukemia, kidney cancer and prostate cancer respectively. They found that all drugs in the series were toxic to cancer cells, with leukemia and kidney cancer cells showing the greatest degree of sensitivity to the hybrid drugs.

To better understand how the hybrid drugs interacted with the Bcr-Abl and HDAC1 active sites (i.e. the ON switch), the team relied on computer-generated three-dimensional models of the hybrid drugs, Bcr-Abl and HDAC1 proteins. Using a method similar to finding the right key for a lock, a computer program found that a hybrid compound termed 6a, which happened to be the most potent compound in the series, fit most snugly into both Bcr-Abl  and HDAC1 active sites. In theory, 6a would prevent both Bcr-Abl and HDAC1 from becoming activated (i.e they remain switched OFF).

On the basis of these observations, this study strengthens the paradigm that chemically melding two cancer drugs to form a novel single molecule may prove to be an effective clinical strategy for anticancer treatment. On a broader scale, this is one among many studies advocating for the use of multi-target agents in cancer treatment, highlighting an imminent upsurge in single molecule combination therapies.

Read the full article here:

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Professor Karen Faulds joins the Editorial Board

A very warm welcome to Professor Karen Faulds!

Karen FauldsPlease join us in extending a very warm welcome to Professor Karen Faulds, as she joins the RSC Advances team as an Editorial Board member!

Karen is a Professor in the Department of Pure and Applied Chemistry at the University of Strathclyde and an expert in the development of surface enhanced Raman scattering (SERS) and other spectroscopic techniques for novel analytical detection strategies. She is the recipient of the Nexxus Young Life Scientist of the Year award (2009), the RSC Joseph Black Award (2013) and the Craver Award from the Coblentz Society (2016). In 2011 was elected to the Royal Society of Edinburgh Young Academy of Scotland (YAS) and was elected Fellow of the Royal Society of Chemistry in 2012. She is the Strathclyde Director of the EPSRC and MRC funded Centre for Doctoral Training in Optical Medical Imaging, OPTIMA and is the current Chair of the Infrared and Raman Discussion Group (IRDG).

Karen is very much looking forward to her new role:

‘I am delighted to be joining the Editorial Board for RSC Advances and look forward to working with the journal, it will be particularly exciting to work with a journal which has a remit which spans the diversity of the chemical sciences’

Karen Faulds and Matthew Baker have recently guest edited a Chemical Society Reviews themed issue on Fundamental Developments in Clinical Infrared and Raman Spectroscopy.

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A hydrogel-based trojan horse for antitumor therapy

Paclitaxel (PTX) is among the most widely used chemotherapeutic agents in clinical settings. The drug imposes its anticancer effect by preventing cell division. Cancer cells learn to resist PTX over time by various mechanisms including creating alterations in the protein targeted by PTX and rewiring of cell survival pathways to evade cell death.

Clinicians combine PTX with suberoylanilide hydroxamic acid (SAHA) to suppress cancer drug resistance and improve treatment outcome. The benefits of combination therapy include improved accumulation of the drug at cancer sites, the ability to trigger cell death by complementary or synergistic mechanisms and longer retention of the drug within patients. Given the strong rationale for combination therapies, Shu and colleagues at the Department of Pharmaceutical Analysis, Key Laboratory on Protein Chemistry and Structural Biology, China developed a novel peptide hydrogel which encapsulates PTX and SAHA within a single co-delivery nano-carrier.

Graphical Abstract for C6RA19917H The researchers loaded PTX and SAHA onto the same nano-carrier in the following sequence: (1) an amino acid-based self assembling hydrogel precursor (Nap) was prepared, (2) PTX was conjugated to the self assembling hydrogel to form a pro-drug and (3) the pro-drug was allowed to encapsulate SAHA, forming the final drug (Nap-PTX-SAHA). The researchers subsequently characterized the mechanical features of their novel drug delivery system and tested it using a mouse model of liver cancer.

The study found that the Nap-PTX-SAHA hydrogels could be injected at room temperature into test mice, suggesting that no specialized equipment or storage conditions were necessary to administer the drug. The study also found that SAHA is released more readily than PTX from Nap-PTX-SAHA hydrogels. This could mean that cancer cells will be exposed to the two chemotherapy agents at different times, allowing for a one-two punch based tumor killing strategy.

When administered to tumor-bearing mice, the Nap-PTX-SAHA regimen was found to decrease tumor volume up to 2-fold compared to mice treated traditionally with PTX or SAHA alone. Interestingly, the researchers also noted that Nap-PTX-SAHA was associated with fewer side effects, as evidenced by normal eating behavior and weight in test mice. Interestingly, Nap-PTX-SAHA was absorbed lesser in non-target organs such as the heart, spleen and kidneys.

On the basis of these promising preclinical studies, the authors propose that Nap-PTX-SAHA represents a promising candidate for clinical trials in the years to come.

Read the full article here:

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Micelles meet transplantation medicine: How a novel nanoparticle based immune cell blocker might benefit human organ transplantation

Organ transplantation saves lives. According to the Organ Procurement and Transplantation Network, U.S Department of Health and Human Services, over 22,000 organs transplantation surgeries have been conducted between January and September 2016.

Ischemia Reperfusion Injury (IRI) is a well characterized cardiac transplantation-related complication wherein the host tissue (graft), deprived of blood supply for prolonged periods, undergoes damage when blood supply is restored post-implantation. Immune cells at the interface of the graft and recipient tissue mediate damage by releasing inflammation-promoting chemicals and free radicals.

In a study led by Nadig and colleagues at the Department of Surgery, Division of Transplant, Medical University of South Carolina, USA, researchers first acknowledge the central role played by endothelial cells (EC) in promoting IRI-associated tissue damage and subsequently developed a novel pH-sensitive, immunosuppressive drug-loaded, targeted micelle nanoparticle to curb the damaging effects of ECs. The team choose rapamycin as their immunosuppressive drug of choice given its dual roles in limiting cytotoxic immune cell functions and in protecting tissues that make up blood vessels.

While treating patients with immunosuppressive drugs prior to surgery is currently a standard practice, a major drawback of this approach is that these drugs prevent immune system activity throughout the body, placing patients at risk for diseases including diabetes and cancer. As an initial step in addressing this limitation, Nadig et al. coated the micelles with cyclic arginine-glycine-aspartate moieties, which specifically bind to and integrin protein (the alpha v beta 3 receptor protein) present almost exclusively on ECs. As a finishing touch, the team attached fluorescent chemical compounds to allow for tracking and visualization in their studies.

Graphical abstract of "Immunosuppressive nano-therapeutic micelles downregulate endothelial cell inflammation and immunogenicity"Their studies showed that the rapamycin-loaded nanoparticles were stable and biocompatible when tested in human endothelial cells. Further, the rapamycin release could be controlled by adjusting the pH values lower than 7 or higher than 8. The study found that the micelles were being taken up by cells within 6h after incubation. The study also demonstrates the specificity of the micelles by showing that what the cells were pre-treated with an integrin inhibitor,  they were  less likely to take up the micelles.

To demonstrate the clinical utility of their idea, the researchers exposed human endothelial cell cultures to hydrogen peroxide to mimic IRI-like conditions. The cells responded by increasing their production of inflammation-promoting chemicals. Importantly, the rapamycin-loaded nanoparticle micelles significantly curbed this response. Nadig et al. propose that the ultimate goal is to incorporate this technology into organ storage media to minimize the harmful effects of IRI.

Read the full article here:

Satish N. Nadig, Suraj K. Dixit, Natalie Levey, Scott Esckilsen, Kayla Miller, William Dennis, Carl Atkinson and Ann-Marie Broome

RSC Adv., 2015, 5, 43552-43562

DOI: 10.1039/C5RA04057D

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Top 10 most-downloaded articles: Q3 July–September 2016

Take a look at the most-downloaded RSC Advances articles from the months of July, August and September 2016 and let us know what you think!

Free radicals, natural antioxidants, and their reaction mechanisms
Satish Balasaheb Nimse and Dilipkumar Pal
RSC Adv., 2015,5, 27986-28006
DOI: 10.1039/C4RA13315C

Size-controlled silver nanoparticles synthesized over the range 5–100 nm using the same protocol and their antibacterial efficacy
Shekhar Agnihotri, Soumyo Mukherji and Suparna Mukherji
RSC Adv., 2014,4, 3974-3983
DOI: 10.1039/C3RA44507K

Synthesis and characterization of magnetic bromochromate hybrid nanomaterials with triphenylphosphine surface-modified iron oxide nanoparticles and their catalytic application in multicomponent reactions
Ali Maleki, Rahmatollah Rahimi, Saied Maleki and Negar Hamidi
RSC Adv., 2014,4, 29765-29771
DOI: 10.1039/C4RA04654D

Thermal-runaway experiments on consumer Li-ion batteries with metal-oxide and olivin-type cathodes
Andrey W. Golubkov, David Fuchs, Julian Wagner, Helmar Wiltsche, Christoph Stangl, Gisela Fauler, Gernot Voitic, Alexander Thaler and Viktor Hacker
RSC Adv., 2014,4, 3633-3642
DOI: 10.1039/C3RA45748F

Synthesis and properties of molybdenum disulphide: from bulk to atomic layers
Intek Song, Chibeom Park and Hee Cheul Choi
RSC Adv., 2015,5, 7495-7514
DOI: 10.1039/C4RA11852A

Graphene and its nanocomposite material based electrochemical sensor platform for dopamine
Alagarsamy Pandikumar, Gregory Thien Soon How, Teo Peik See, Fatin Saiha Omar, Subramaniam Jayabal, Khosro Zangeneh Kamali, Norazriena Yusoff, Asilah Jamil, Ramasamy Ramaraj, Swamidoss Abraham John, Hong Ngee Lim and Nay Ming Huang
RSC Adv., 2014,4, 63296-63323
DOI: 10.1039/C4RA13777A

Dual protection of amino functions involving Boc
Ulf Ragnarsson and Leif Grehn
RSC Adv., 2013,3, 18691-18697
DOI: 10.1039/C3RA42956C

Electrically conductive polymers and composites for biomedical applications
Gagan Kaur, Raju Adhikari, Peter Cass, Mark Bown and Pathiraja Gunatillake
RSC Adv., 2015,5, 37553-37567
DOI: 10.1039/C5RA01851J

Colloidal semiconductor nanocrystals: controlled synthesis and surface chemistry in organic media
Jin Chang and Eric R. Waclawik
RSC Adv., 2014,4, 23505-23527
DOI: 10.1039/C4RA02684E

Anti-bacterial surfaces: natural agents, mechanisms of action, and plasma surface modification
K. Bazaka, M. V. Jacob, W. Chrzanowski and K. Ostrikov
RSC Adv., 2015,5, 48739-48759
DOI: 10.1039/C4RA17244B

Interesting in submitting to RSC Advances? You can submit online today, or email us with your ideas and suggestions.

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RSC Advances: Recognising our reviewers

This week, the Royal Society of Chemistry has been joining in the celebrations for Peer Review Week – a global event recognising the essential role that peer review plays in maintaining scientific quality.

At RSC Advances, recognising our reviewers is very important to us. Earlier this year we launched the RSC Advances Reviewer Panel, containing almost 450 members from over 50 countries, spread across 6 continents.  Members of the Reviewer Panel are hand-picked by the editors and are specialists from across all fields of the chemical sciences. They are a key part of our commitment to deliver rigorous and fair peer review and that your manuscript is handled by experts throughout the peer review process. We are proud to work with these individuals and to recognise their crucial role, their names are published on our website and they receive a certificate, thanking them for their hard work, dedication and valuable contribution they have made to the journal.

Our Associate Editors also play an important role in our peer review process providing reviews on manuscripts they are handling that are in their area of expertise. The Associate Editors receive payment for the manuscripts they handle as part of our recognition of the central role they have in maintaining the strict scientific and quality standards of RSC Advances.

We would like to say a massive thank you to our Associate Editors and Reviewer Panel members, as well as the RSC Advances Editorial Board, and all of the chemical sciences community for their continued support of the journal, as authors, reviewers and readers.

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Sticks and stones may break my bones, but hydrogels will never hurt me

Recent advancements in tissue engineering have led to the fabrication of complex materials that may be used as surrogates for heart, neuronal, bone and cartilage tissue regeneration. A vast majority of engineered tissues are composed of a three-dimensional scaffold at its core, layered with growth stimulating agents, that collectively nurture and support cell growth.

In a study by Gantar and colleagues at the Jozef Stefan Institute, Department for Nanostructured Materials in Slovenia,  a team of researchers created an injectable hydrogel as a potential biomaterial for bone tissue regeneration. They further demonstrate that the hydrogel is capable of self-healing and supports the growth of cells derived from human bone tissue.

Hydrogels based on reversible covalent bonds allow the material to rearrange its structure permanently. This forms the basis for self-healing. A potential drawback is that the conditions (temperature and pH) required to form these bonds to form are not suitable for supporting bone cell growth. Having recognized this limitation, the team decided to develop a liquid hydrogel that transitions to a gel-like state at a pH suitable for cell growth and proliferation. Further, the hydrogel was infused with bioactive glass (BAG) nanoparticles – a silica-based material known to support bone cell growth.

The study also characterizes the physical (elastic properties, compression) and biological (degradation, cytotoxicity) features of the injectable hydrogel. The study finds that the BAG nanoparticles do not drastically alter the physical and biological properties of the hydrogel and suggest that the combination is well suited to support bone cell growth. The team proposes that their efforts will contribute toward the development of an injectable material that will scaffold bone cells within the host and promote self-repair.

Read the full article here:

Injectable and self-healing dynamic hydrogel containing bioactive glass nanoparticles as a potential biomaterial for bone regeneration
Ana Gantar, Nataša Drnovšek, Pablo Casuso, Adrián Pérez-San Vicente, Javier Rodriguez,c   Damien Dupin, Saša Novakab and Iraida Loinazc
RSC Adv., 2016,6, 69156-69166
DOI: 10.1039/C6RA17327F

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It’s in the blood

Written by Harriet Brewerton

Scientists have designed a tiny fuel cell that generates electricity from the human body’s blood flow, and for the first time, they have tested the device in a person.

The blood-powered fuel cell connected to a low voltage display

The blood-powered fuel cell connected to a low voltage display

Phones, tablets and other portable electronics are common, but development of equally portable power sources is lagging behind. This is a particular concern for biomedical devices such as pacemakers. Since the 1960s, researchers have made biocompatible fuel cells that generate power inside the body. However, none of these power sources has been successfully demonstrated in a human subject.

To read the full article visit Chemistry World.

Ex vivo electric power generation in human blood using an enzymatic fuel cell in a vein replica
Dmitry Pankratov, Lars Ohlsson, Petri Gudmundsson, Sanela Halak, Lennart Ljunggren, Zoltan Blum and Sergey Shleev
RSC Adv., 2016,6, 70215-70220
DOI: 10.1039/C6RA17122B, Communication

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A study on spheroid formation in thermosensitive hydrogels

According to an estimate by the World Cancer Report, cancer associated mortality is expected to reach 17 million per year globally by the year 2030. To confront the cancer burden with appropriate clinical interventions, researchers screen cancer-killing drug combinations in monolayer cell cultures. This is a widely used method for the preclinical evaluation of drug efficacy.

A major limitation of monolayer cultures is that they do not, even mildly, recapitulate the complex architecture of a tumor growing in vivo. As an initial step in overcoming this limitation, researchers use scaffolded spheroid cultures – a system wherein cells are grown on hydrogel scaffolds in three dimensions.

Hydrogel scaffolds provide physical and structural support for the formation of a more ‘natural’ setting that better recapitulates cell behavior in vivo. For example, smaller (150um) spheroids have better cell-to-cell contacts and notably different gene expression compared to monolayer cultures; larger (200-500um) ones develop oxygen and nutrient gradients reminiscent of chemical gradients seen in human tumors. However, limitations in design flexibility, handling and interbatch compositional variation have discouraged the routine use of hydrogel scaffolds. In addition, the technical challenge of separating newly formed spheroids from the scaffolding material before drug screening represents a major roadblock.

In a study led by Xiaolin Cui and colleagues at the School of Chemical Engineering and the School of Mathematical Sciences, University of Adelaide, Australia, researchers synthesized a thermo-reversible N-Isopropylacrylamide-acrylic acid (NIPAM-AA) hydrogel by free radical emulsion polymerization. In their study using the cervical carcinoma cell line HeLa, the team demonstrates that at 370C the NIPAM-AA hydrogel solidifies and forms a sheath around HeLa cell clusters. As a consequence, these clusters develop into hydrogel scaffolded spheroids over time. At 250C the hydrogel liquefies and releases the newly formed spheroids.

Cell viability assays confirmed that this new state of the art hydrogel is biocompatible. NIPAM-AA derived spheroids were smaller (70-120um),  nearly spherical and showed a narrower size distribution compared to conventional spheroids. The study showed, through time course experiments, that the spheroids remain viable for over 14 days in culture. The study also suggests that spheroids derived via the NIPAM-AA hydrogel method are more viable than those derived from conventional suspension cultures, supporting the notion that hydrogel scaffolding facilitates oxygen and nutrient supply to support cell growth.

The researchers deduced a mathematical model to predict the kinetics of NIPAM-AA derived spheroid growth. Their model accurately recapitulated the growth rate, size and size distribution of the spheroids. The authors propose that hydrogel scaffolding has the potential to evolve into a technology with a wide range of applications including, but not limited to, (1) high throughput screening of anticancer drugs using uniformly sized spheroids; (2) regenerative medicine; and (3) tissue engineering.

Read the full article here:

Xiaolin Cui,   Saber Dini,   Sheng Dai,   Jingxiu Bi,   Benjamin Binder,   Edward Green and   Hu Zhang
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