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

13 Oct 2016

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:

Immunosuppressive nano-therapeutic micelles downregulate endothelial cell inflammation and immunogenicity

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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Now you see me: autofluorescent nanoparticles for live cell imaging and biodegradation modeling

03 Jun 2016

There is an increasing need for novel technologies to facilitate in vivo tissue visualization and drug delivery. However, this need is largely unmet due to the challenges associated with creating biocompatible materials that meet safety standards. In addition, the potential health risks associated with the accumulation of non-degradable imaging agents and drug carries represents a major obstacle in the innovation pipeline.

The intrinsic autofluorescent, biodegradable and biocompatible properties of Bovine Serum Albumin (BSA) is well appreciated. However, BSA has short excitation and emission wavelengths, which substantially restricts any in vivo biomedical applications. Motivated by a recent report suggesting that glutaraldehyde (GA)-crosslinking induces autofluorescence in protein-based nanoparticles by modifying a series of C=C and C=N bonds, a team led by Yu Lei at the Department of Biomedical Engineering, University of Connecticut, developed low-cost, non-toxic, BSA-based protein nanoparticles (average size ~40 nm) for live cell imaging and biodegradation analysis.

The nanoparticles were generated by adding drops of a prepared BSA solution to glutaraldehyde/n-butanol solution at high-speed, and the resulting product heated at 121°C to ensure sterility. Interestingly, a similar reaction carried out in the absence of the GA crosslinker did not produce autofluorescent BSA nanoparticles, suggesting that GA was indeed playing an important role in chemically transforming BSA. Using UV-visible spectroscopy, the investigators observed that BSA nanoparticles exhibited strong autofluorescence at both green (530 nm) and red (630 nm) wavelengths.

The BSA nanoparticles were not uniform in structure, owing to the random points of crosslinking within BSA, and also due to the ensuing condensation reaction that occurs during the sterilization step. Therefore, a clear mechanistic explanation for the strong autofluorescence warrants further investigation. However, the investigators speculate that GA-crosslinking and heating could result in new C=N bonds, which could synergize with the C=C bonds from tryptophan, tyrosine, phenylalanine and histidine residues with BSA, leading to enhanced green and red fluorescence.

The team went on to demonstrate the utility of the BSA nanoparticles in biomedical applications such as imaging and biodegradation. They used fluorescent microscopy techniques to visualize the entry of BSA nanoparticles into human kidney cells grown in vitro. The study also found that the BSA nanoparticles were completely degraded within 18 days of injection in mice. A mathematical model for the distribution and biodegradation of the nanoparticles was in good agreement with the experimental results. Finally, to add an additional line of evidence supporting the biocompatible nature of the BSA nanoparticles, the investigators looked for signs of tissue damage in the region surrounding the site of injection, together with an analysis of internal organs including the pancreas, liver and kidney, and report that the BSA nanoparticles are biocompatible.

Read the full article here:

Novel green and red autofluorescent protein nanoparticles for cell imaging and in vivo biodegradation imaging and modeling

Xiaoyu Ma, Derek Hargrove, Qiuchen Dong, Donghui Song, Jun Chen, Shiyao Wang, Xiuling Lu, Yong Ku Cho, Tai-Hsi Fan and Yu Lei

DOI: 10.1039/c6ra06783b

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Modelling lung cancer: tumor cells on collagen scaffolds

13 Apr 2016

Non-small-cell lung cancer (NSCLC) is among the leading causes of cancer-related deaths globally. Our understanding of the way tumors grow, spread and respond to therapy is driven largely by studies conducted on tumor cells growing as monolayers in plastic cell culture flasks in laboratories across the world. The ability to develop novel and more effective cancer-fighting drugs is dependent, in part, on developing cell culture systems that allow scientists to better observe how tumor cells grow in a three dimensional, physiologically relevant environment.


	SEM images of the collagen meshwork and A549 cell aggregates (noted by the arrow head) formed during the 3D cultivation in vitro.

The tumor microenvironment (TM) is the area that immediately surrounds a tumor and includes non-cancer cells together with secreted proteins called the extracellular matrix (ECM), which supports tumor growth. Monolayer cell cultures, although utilized widely, cannot accurately mimic the TM. For instance, cell-cell and cell-ECM interactions that influence tumor growth cannot be observed in great detail with conventional monolayer cultures. Inspired by the up-and-coming field of tumor engineering, which aims to construct culture models that recapitulate aspects of the TM, a team of researchers led by Dr. Dan-Dan Wang at the Chinese Academy of Sciences developed a 3D culture system wherein A549 cells (immortal lung cancer cells of human origin) grow on a collagen hydrogel scaffold.

To demonstrate the utility of the 3D culture system, the study measured cell viability and showed that cells in the collagen hydrogel scaffold were alive for extended periods (>12 days) in vitro. The study also assessed the appearance of artificial A549 tumors growing on the hydrogel to demonstrate that 3D cultures more closely recapitulate the morphology of tumors growing within human tissues.

The proliferation of A549 cells is driven by the activation of a cell surface protein called Epidermal Growth Factor Receptor (EGFR), which in turn switches on genes that sustain cell growth and cell division. The team observed that Gefitinib, a drug known to disrupt growth-promoting signals arising at EGFR, was able to significantly constrain A549 cell proliferation in 3D cultures. Interestingly, the team reports that a higher concentration of Gefitinib was required to curb cell growth in 3D cultures compared to monolayers due to the complex architecture of the artificial tumors in 3D cultures.

Collectively, this study demonstrates an improved culture model of human lung cancer. Since collagen is an important component of the ECM, the study sets the stage for future efforts to better recapitulate the TM in vitro. The collagen hydrogel scaffold system could serve as in important tool in the discovery of targeted therapies for lung cancer.

Read the full article here:

Bioengineering three-dimensional culture model of human lung cancer cells: an improved tool for screening EGFR targeted inhibitors

Dan-Dan Wang, Wei Liu, Jing-Jie Chang, Xu Cheng, Xiu-Zhen Zhang, Hong Xu, Di Feng, Li-Jun Yu and Xiu-Li Wang

RSC Adv., 2016, 6, 24083-24090

DOI: 10.1039/C6RA00229C

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Introducing the organic chemistry collection

23 Feb 2016

This organic chemisty collection has been collated by Editorial Board member Professor Russell Cox (Leibniz University Hannover, Germany). It brings together articles with the continued aim of inspiring new authors to submit their best work to the journal, and also to highlight great work by regular authors. These articles are already among the most highly cited works in the journal, illustrating their impact.

The subject areas of the articles include those traditionally regarded as organic, such as synthesis, catalysis, heterocyclic and organometallic chemistry, natural products chemistry and method development. In addition, the collection also includes articles from overlapping areas, such as green chemistry, fuel production, ionic solvents and materials chemistry, where there is a strong organic and biological component. Underpinning all are theoretical and computational studies. Finally, emerging areas, including photovoltaics and chemical biology, have strong organic chemistry foundations and also find a natural home in this RSC Advances collection.

This selection aims to illustrate the breadth, depth and impact of papers published in RSC Advances in the area of organic chemistry and stimulate new submissions in these and allied areas.

The collection contains reviews, communications and full papers, all of which can be found here.

Credit: Recent advances in 4(3H)-quinazolinone syntheses, 10.1039/C4RA00351A

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Reviewer Panel Member Terms of Reference

01 Dec 2015

RSC Advances
Reviewer Panel Member

TERMS OF REFERENCE

Role
To be a member of the RSC Advances Reviewer Panel and provide 24, 36 or 48 reviews per year.

You will be invited by Associate Editors to review submissions in your selected area(s) of expertise. Associate Editors will use your chosen areas of expertise, along with subject areas provided by authors during submission of their manuscript, to invite you to review suitable manuscripts.

Responsibilities of a Reviewer Panel Member

To act as a reviewer for RSC Advances. Panel members can expect to receive, on average, from two to four manuscripts to review per month within their field of expertise.
To advise and assist the RSC Advances Associate Editors in assessing manuscripts against the publication criteria of the Journal (see below) and to recommend suitable papers for publication in RSC Advances.
To provide a recommendation and report via the manuscript processing system within the timeframe specified on the reviewer invitation email.
To provide advice to the RSC Advances Associate Editors on borderline papers and act as adjudicator in cases involving conflicting reviewer reports and appeals where appropriate.
To inform the Associate Editor, by responding appropriately to the reviewer invitation, if a manuscript sent to you for review cannot be assessed for any reason (including conflicts of interest) and where possible suggest an alternative member of the Reviewer Panel.
To notify the Editorial Office, in advance, of any significant periods of time that you will be unavailable for reviewing.
To regularly update your research interests via the manuscript processing system (http://mc.manuscriptcentral.com/rscadv).

Criteria for publication in RSC Advances

When assessing articles for publication in RSC Advances, please consider the following:

Does the work present a significant advance over the existing literature? Is the advance clearly highlighted in the main article?
Has sufficient evidence/data been provided to support the conclusions of the work?
Has adequate characterisation data been provided for any materials/compounds that are reported? For full details, please see the “Characterisation of new compounds” section within our Journal’s webpage here: http://www.rsc.org/journals-books-databases/about-journals/rsc-advances/
Are the results discussed in the context of the literature?
Are the references relevant and do they appropriately reflect the existing literature?
Do the figures and tables in the paper assist the reader in understanding the work? Are the structures of any compounds presented accurately drawn?

Recognition of services

As member of the RSC Advances Reviewer Panel your name will be displayed on the Journal’s website.

In recognition of the service you are providing, members of the RSC Advances Reviewer Panel will be issued with a certificate at the end of each year highlighting the valuable contribution you have made to the Journal.

Term

Membership of the Reviewer Panel is on a rolling basis from the date of your enrolment. If you wish to resign from the Reviewer Panel please contact the Editorial Office.

The Editorial Office will review your membership against the responsibilities listed above on an annual basis.

Confidentiality

The Panel Member shall keep strictly confidential all information which comes into his/her possession as a result of carrying out the activities specified herein which in any way relates to the business of the Royal Society of Chemistry. This obligation shall have no effect in relation to any such information which is (i) already known to him/her at the time of its disclosure to him/her or (ii) public knowledge or becomes so without his/her fault or (iii) disclosed to him/her subsequently by a third person or (iv) required to be disclosed by order of any court of competent jurisdiction or governmental authority.

Intellectual Property Rights

All material produced by you while carrying out your role as a Panel Member belongs to the Royal Society of Chemistry. The Royal Society of Chemistry retains the sole right and licence to publish such material in any format (including electronic) and to sub-license a third party to publish the material. The Panel Member must ensure that the material does not infringe the copyright of others.

Any articles submitted by you as an author or co-author for publication in any Royal Society of Chemistry journal are not covered by these arrangements. Any such articles will be dealt with according to the usual Royal Society of Chemistry publishing procedures and will require a signed “Licence to Publish” to be completed for each submission.

Data Protection

As a Panel Member you must protect the personal data of individuals, both members and non-members, in accordance with the provisions and principles of the Data Protection Act 1998. “Personal data” has the same meaning as in the Data Protection Act 1998.

Queries

If you have any queries, please do not hesitate to contact the Editorial Office at:
advances-rsc@rsc.org – for queries regarding this role; or
advances@rsc.org – for all queries relating to specific manuscripts or using ScholarOne.

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Subject Area & Keyword selection during your manuscript submission

16 Oct 2015

Our new peer review process for RSC Advances means that you can be sure your work will be in the safe hands of an expert, every step of the way.

To help ensure that your manuscript will be assigned to an appropriate Associate Editor, we’re now asking you, our authors, to select a Subject Area and Keyword during the manuscript submission process online.

During the submission of your manuscript, simply use the drop-down menu, as shown below, to pick the Subject Area and Keyword that best describes your work.

Subject Area and Keyword selection

Submit your manuscript online now!

For pre-submission queries, please feel free to send us an email.

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Does size matter? Rational design of potent ice recrystallization inhibitors

02 Oct 2014

Ice recrystallization inhibition (IRI) activity is a highly desirable property for an effective cryoprotectant. Cryopreservation is a very important process for regenerative medicine therapies, but ice recrystallization causes reduced post thaw cell viability. Although antifreeze proteins (AFPs) and antifreeze glycoproteins (AFGPs) were first investigated as cryoprotectants, their ability to bind and alter the ice crystals behaviour has encouraged researchers to look for further improvement in this field. This has led to the development of AFGP to AFGP analogues and further to the discovery of small carbohydrate-based IRIs with similar IRI activity to that of native AFGP-8.

In this review, Robert Ben and co-workers from the University of Ottawa, Canada, present recent developments of IRIs mainly focusing on novel small molecules that have emerged as potential cryoprotectants.

Designing ice recrystallization inhibitors: from antifreeze (glyco)proteins to small molecules

They begin with the molecular mechanism of the ice recrystallization phenomenon and it’s relation with IRI activities of biological antifreezes. The recent strategies for improving antifreeze compounds have been thoroughly discussed including large protein or peptide analogues, easily accessible synthetic polymers, simple mono- and disaccharide derivatives, truncated C-linked glycopeptides and carbohydrate or lysine-based surfactants/gelators. This review nicely highlights the importance of hydration index, relative orientation of hydrophilic groups and size of the linker of synthetic antifreeze compounds on their overall IRI activity.

In future these kinds of highly IRI active small molecules may replace the most widely used cytotoxic cryoprotectant DMSO and improve upon currently limited cryopreservation protocols.

Read the full review in RSC Advances – free to access for 4 weeks:

Designing ice recrystallization inhibitors: from antifreeze (glyco)proteins to small molecules

Anna K. Balcerzak, Chantelle J. Capicciotti, Jennie G. Briard and Robert N. Ben, RSC Adv., 2014, 4, 42682-42696

You may also be interested in these related articles:

The importance of hydrophobic moieties in ice recrystallization inhibitors

Anna K. Balcerzak, Michela Febbraro and Robert N. Ben, RSC Adv., 2013, 3, 3232-3236

Developing highly active small molecule ice recrystallization inhibitors based upon C-linked antifreeze glycoprotein analogues

John F. Trant, Robyn A. Biggs, Chantelle J. Capicciotti and Robert N. Ben, RSC Adv., 2013, 3, 26005-26009

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Cystic fibrosis treatment clears the way

18 Mar 2014

Stabilising a mucus attacking enzyme with cross-links could allow it to be delivered orally to fight infections in cystic fibrosis patients.

Pseudomonas aeruginosa is one of the commonest opportunistic pathogens in cystic fibrosis. The bacterium produces alginate, a polysaccharide which causes significant mucus build-up in the lungs and intestine. In addition to affecting patients’ quality of life, this also significantly obstructs the delivery of antibiotics, requiring increased dosages which can lead to antibiotic resistance and an increased chance of side-effects.

Guillermo Castro at the National University of La Plata in Argentina, and his team, investigate the delivery of drugs with significant administrative problems’…

Interested? If so, read the full article at Chemistry World here.

Cross-linking alginate lyase in the presence of BSA stabilises the enzyme but leaves the active site intact

Please click on the below title to access the original article which is free to access until 7^th April 2014 :

Development of novel alginate lyase cross-linked aggregates for the oral treatment of cystic fibrosis
G. A. Islan, Y. N. Martinez, A. Illanes and G. R. Castro
RSC Adv., 2014, 4, 11758-11765
DOI: 10.1039/C3RA47850E

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‘HOT’ articles!

10 Mar 2014

Our referees have spoken once again and chosen the below ‘HOT’ articles. Please have a gander and let us know what you think in the comments section below:

Mn²⁺/graphene oxide nanocomposite efficiently catalyzes the epoxidation of alkenes with H₂O₂
Weiguo Zheng, Rong Tan, Lili Zhao, Yaju Chen, Chuanwu Xiong and Donghong Yin
RSC Adv., 2014, 4, 11732-11739
DOI: 10.1039/C3RA47183G

Enzymatic oxidation as a potential new route to produce polysaccharide aerogels
Kirsi S. Mikkonen, Kirsti Parikka, Jussi-Petteri Suuronen, Abdul Ghafar, Ritva Serimaa and Maija Tenkanen
RSC Adv., 2014, 4, 11884-11892
DOI: 10.1039/C3RA47440B

Sensitive and regenerable organochalcogen probes for the colorimetric detection of thiols
Shah Jaimin Balkrishna, Ananda S. Hodage, Shailesh Kumar, Piyush Panini and Sangit Kumar
RSC Adv., 2014, 4, 11535-11538
DOI: 10.1039/C4RA00381K

And remember – these articles are free to access for 4 weeks!

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RSC Advances Blog

Archive for the ‘Uncategorized’ Category

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

Now you see me: autofluorescent nanoparticles for live cell imaging and biodegradation modeling

Modelling lung cancer: tumor cells on collagen scaffolds

Introducing the organic chemistry collection

Reviewer Panel Member Terms of Reference

Top 10 most-downloaded articles: Q3 July–September 2015

Subject Area & Keyword selection during your manuscript submission

Does size matter? Rational design of potent ice recrystallization inhibitors

Cystic fibrosis treatment clears the way

‘HOT’ articles!

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