Category Archives: MQ

New X-ray-induced photodynamic therapy system

19 June 2018:

Researchers from CNBP have developed an X-ray-induced photodynamic therapy (PDT) system where nanoparticles incorporating a photosensitizer, verteporfin, were triggered by X-ray radiation to generate cytotoxic singlet oxygen. This system offers the possibility of enhancing the radiation therapy commonly prescribed for the treatment of cancer by simultaneous PDT.

Lead author on the paper was Dr Sandhya Clement (pictured).

Journal: International Journal of Nanomedicine.

Publication title: X-ray radiation-induced and targeted photodynamic therapy with folic acid-conjugated biodegradable nanoconstructs.

Authors: Sandhya Clement, Wenjie Chen, Wei Deng, Ewa M Goldys.

Abstract:
Introduction: The depth limitation of conventional photodynamic therapy (PDT) with visible electromagnetic radiation represents a challenge for the treatment of deep-seated tumors. Materials and methods: To overcome this issue, we developed an X-ray-induced PDT system where poly(lactide-co-glycolide) (PLGA) polymeric nanoparticles (NPs) incorporating a photosensitizer (PS), verteporfin (VP), were triggered by 6 MeV X-ray radiation to generate cytotoxic singlet oxygen. The X-ray radiation used in this study allows this system to breakthrough the PDT depth barrier due to excellent penetration of 6 MeV X-ray radiation through biological tissue. In addition, the conjugation of our NPs with folic acid moieties enables specific targeting of HCT116 cancer cells that overexpress the folate receptors. We carried out physiochemical characterization of PLGA NPs, such as size distribution, zeta potential, morphology and in vitro release of VP. Cellular uptake activity and cell-killing effect of these NPs were also evaluated. Results and discussion: Our results indicate that our nanoconstructs triggered by 6 MeV X-ray radiation yield enhanced PDT efficacy compared with the radiation alone. We attributed the X-ray-induced singlet oxygen generation from the PS, VP, to photoexcitation by Cherenkov radiation and/or reactive oxygen species generation facilitated by energetic secondary electrons produced in the tissue. Conclusion: The cytotoxic effect caused by VP offers the possibility of enhancing the radiation therapy commonly prescribed for the treatment of cancer by simultaneous PDT.

 

CNBP science gets fresh

6 June 2018:

CNBP researcher Dr Annemarie Nadort has participated in ‘Fresh Science’, a national competition helping early-career researchers find, and then share, their stories of discovery. The program takes up-and-coming researchers with no media experience and turns them into spokespeople for science, giving them media training and a public event to present their science to the community. Ten researchers took part in the Fresh Science event for NSW.

Dr Nadort reports on her experience below.

“Fresh Science was an intense, colourful, and informative workshop ranging between fun and hard work. The first day consisted of a Q&A and mock interviews with journalists from television, radio and written news. The participants all had very interesting and new science to pitch and I definitely enhanced my network of Sydney researchers.”

“I also was impressed by the skills of the journalists. They said that society viewed them as the least trusted people, but their professionalism and ability to pick up the most important parts of our complicated science made me think the opposite!”

“The second morning consisted of a Q&A with commercialisation experts, the NSW Chief Scientist and collaboration experts, followed by a 1 minute pitch to stakeholders.”

“The workshop concluded with a final event at the Three Wise Monkeys Hotel: every Fresh Scientist presented their research for as long as their sparkler was still sparkling.”

“I was awarded the ‘highly commended’ distinction for my ‘bright sparks’ presentation which detailed the development of optical methods to improve the detection and therapy of high-grade brain cancer.”

Below – Dr Annemarie Nadort presents her science to an interested and engaged audience at the Three Wise Monkeys Hotel, Sydney.

CNBP outreach at MQ ‘Career Ready Day’

10 May 2018:

CNBP’s Dr Annemarie Nadort has shone a light on biophotonics, microcirculation, medical device development and a career in science to an audience of 35 Yr 9-10 high school students, at an outreach session at Macquarie University, May 10th, 2018.

The students, attending the University as a part of a ‘career-ready’ day, were given a quick tutorial on blood and light and were then given a hands-on demonstration of a clinical microcirculation imager that was able to provide a real-time view of red blood cells circulating in capillaries under the tongue.

Students were then given a brief history of the imager’s development and then asked how they could potentially improve a mark-two version of the device from a biological, physics, engineering, IT and software perspective. This explained Dr Nadort was the sort of critical thinking required to kick-start a career in medical device design and development; and the skills that could be learnt from undertaking higher education study.

Feedback from the students was extremely positive. Half a dozen students tried the imager under their own tongues. Seeing the body’s cells operate in real-time on a large screen proved insightful and engaging to all in the room.

Below – Dr Annemarie Nadort explains to students how we can use light to see blood using innovative new tools and techniques.

Detecting zearalenone (a toxin found in cereals)

1 May 2018:

CNBP PhD student at Macquarie University, Fuyuan Zhang (pictured), is first author on a new paper reporting on the development of magnetic nanobead based fluoroimmunoassays  for detection of zearalenone (a toxin found in cereals).

Journal: Sensors and Actuators B: Chemical.

Publication title: Novel magnetic nanobeads-based fluoroimmunoassays for zearalenone detection in cereals using protein G as the recognition linker.

Authors: Fuyuan Zhang, Bing Liu, Guozhen Liu, Wei Sheng, Yan Zhang, Qi Liu, Shuo Wang.

Abstract: Zearalenone (ZEN) is a type of estrogenic mycotoxin commonly found in cereals. In order to satisfy the need for ultrasensitive detection of ZEN, we developed two novel magnetic nanobeads (MNBs)-based fluoroimmunoassays using protein G (PG) as recognition binder on the sensing interface. One proposed facile strategy is based on a first capture last react (FCLR) procedure while the other is a first react last capture (FRLC) format. Specifically, CdTe/CdS/ZnS quantum dots were synthesized and modified to antigen (OVA-ZEN) as the signal probes. The PG modified MNBs specifically captured the fragment crystallizable region of immunoglobulin G (IgG) with a level of orientation while avoiding the destruction of antibody’s binding sites caused by chemical coupling. Under the optimized conditions, the detection limits of 0.019 ng mL−1 and 0.049 ng mL−1 in the extract solution were obtained for the FCLR and FRLC, respectively. Furthermore, the established methods proved to be successful in detecting ZEN in real cereal samples with the detection limits being 0.6 μg kg−1 and 1.5 μg kg−1 in the FCLR and FRLC, respectively. The performance of the proposed assays was evaluated utilizing commercial ELISA kits with satisfactory results.

New CNBP review paper on SERS

23 April 2018:

CNBP researchers have  published a new review paper on surface enhanced Raman scattering (SERS), reporting on recent developments and applications, and in particular examining SERS nanotags in biosensing and bioimaging, describing case studies in which differing types of biomarkers have been investigated. Lead author on the paper was Wei Zhang from Macquarie University.

Journal: Journal of Analysis and Testing.

Publication title: SERS Nanotags and Their Applications in Biosensing and Bioimaging.

Authors: Wei Zhang, Lianmei Jiang, James A. Piper, Yuling Wang.

Abstract: Owing to the unique advantages of surface enhanced Raman scattering (SERS) in high sensitivity, specifcity, multiplexing capability and photostability, it has been widely used in many applications, among which SERS biosensing and bioimaging are the focus in recent years. The successful applications of SERS for non-invasive biomarker detection and bioimaging under in vitro, in vivo and ex vivo conditions, ofer signifcant clinical  information to improve diagnostic and prognostic outcomes. This review provides recent developments and applications of SERS, in particular SERS nanotags in biosensing
and bioimaging, describing case studies in which diferent types of biomarkers have been investigated, as well as outlining future challenges that need to be addressed before SERS sees both pathological and clinical use.

Centre outreach encourages a career in science

18 April 2018:

Two fantastic sessions of outreach in two days by CNBP researcher Dr Annemarie Nadort saw 100 Year 11 and Year 12 students learn about biophotonics, blood cells and the skills required to create medical devices that benefit society.

The sessions took place at Macquarie University and were part of a highly successful initiative aimed at encouraging students to undertake higher education learning and potentially develop a career in science.

During the outreach sessions, Dr Annemarie Nadort provided the students with a brief overview of light-based imaging and how it could be best applied to examine blood inside the body. Students were then presented with a real-life case-study on the development of a clinical microcirculation imager. A hands-on demonstration of the device then took place, followed by an interactive group discussion on how the device could be potentially improved with future development. Students were then left with the message that there were many opportunities open to them across the scientific and technology disciplines,  and that they should study in those areas that they were most enthusiastic about.

“I was extremely impressed as to how engaged these students were,” said Dr Annemarie Nadort. “They provided some great answers during the group discussion stage of the session and had really thought through issues and potential solutions. I could see the keenness for science and technology in the room and hopefully my sessions added to that keenness and passion for science. I’d love to see some of these students become the researchers of the future, developing their own fantastic new medical devices over the years and decades to come.”

Below: Dr Annemarie Nadort communicating the wonders of science to high school students and explaining what it takes to become a successful academic research scientist.

Advanced sensor to unlock the secrets of the brain

17 April 2018:

CNBP researchers have announced the development of a state-of-the-art sensor that can for the first time detect signalling molecules, called cytokines, which operate in the living brain. Cytokines in the brain are secreted by glia cells that make up nearly 90% of all brain cells. Cytokines play a central role in controlling mood and cognition and may also contribute to a number of mental health disorders.

“What we’ve developed is the first sensor capable of monitoring the release of these cytokines in the brain,” says lead researcher Kaixin Zhang, a PhD candidate at the ARC Centre of Excellence for Nanoscale BioPhotonics (CNBP) at Macquarie University.

“Critically, there is mounting evidence that these glial-released cytokines play a central role in regulating a range of brain functions. In particular they are responsible for affecting mood, cognition and behaviour.”

“Our innovative new sensor has the potential to increase our knowledge not only of how the brain works, but may be able to shed light on conditions such as depression, stress, anxiety and even schizophrenia,” he says.

The sensor consists of a modified optical fibre which has had its surface treated with a capture protein. The protein reacts to the presence of cytokine molecules and is capable of monitoring local cytokine release in discrete and targeted parts of the brain.

Professor Ewa Goldys, CNBP Deputy Director, and a senior researcher on the project, notes that brain functionality is an extremely complex area where scientific knowledge is still limited.

“Our research in understanding cytokine secretion, neural circuits and how these two work together is essential to improving our understanding of the brain, in health and disease. Our sensor has opened a new window to the brain, but we still have far more to discover,” she says.

“The key benefit of our new sensor is that it enables the detection of cytokine release precisely as it happens, in living, naturally behaving animals, which is the key step on this discovery journey. To date, suitable tools have not been available to do this as the living brain is an incredibly difficult part of the body to access, and these cytokines are very difficult to measure.”

Published in the leading scientific journal ‘Brain, Behavior, and Immunity’, the cytokine sensor research was undertaken by an international team of scientists at the ARC Centre of Excellence for Nanoscale BioPhotonics (CNBP), Macquarie University, University of Colorado Boulder, Central China Normal University and The University of Adelaide.

“This is a really fantastic example of the work which we do at the CNBP, which is all about creating state-of-the-art sensing tools that can measure the inner workings of the living organism,” says Prof Goldys.

“It may be early days in this research but it will be fascinating to see where this cytokine detection takes us. It may prove to be a pivotal point in the understanding, and eventual diagnostic and clinical treatment, of a whole range of health conditions.”

PAPER:
A novel platform for in vivo detection of cytokine release within discrete brain regions. https://www.sciencedirect.com/science/article/pii/S0889159118301302

AUTHORS: Kaixin Zhang, Michael V. Baratta, Guozhen Liu, Matthew G. Frank, Nathan R. Leslie, Linda R. Watkins, Steven F. Maier, Mark R. Hutchinson, Ewa M. Goldys.

Below – CNBP PhD Candidate – Kaixin Zhang.

Successful BioNetwork 2018 symposium

13 April 2018:

The BioNetwork 2018 symposium titled ‘Killing it in Science’ was held Friday, 13th April at Macquarie University with significant CNBP involvement at the event.

The aim of the symposium was to foster interactions across the Macquarie University biosciences researcher community encompassing the Science & Engineering and Medicine & Health Sciences Faculties.

A unique career-building panel session was held in the morning of the symposium and a scientific session was held in the afternoon to create a platform for interdisciplinary research collaborations to commence novel or strengthen existing projects.

CNBP Associate Investigators Dr Alfonso Garcia-Bennett (Macquarie University) and Dr Varun Sreenivasan (University of New South Wales) were both invited speakers at the event speaking to their careers in academia, providing tips for advancement as well as outlining challenges that they had faced.

For the science session, CNBP students Mina Ghanimi Fard and Sameera Iqbal (pictured top left) jointly presented on the brain and the targeting and measuring of central nervous system sugar receptors. Other CNBP students also took part with Piotr Wargocki, Kashif Islam, Minakshi Das and Rachit Bansal presenting their CNBP releated science during the morning and lunch-time poster sessions.

CNBP AI’s Annemarie Nadort and Nima Sayyadi were both key members of the symposium organising committee.

“We had a fantastic engaged crowd of over 150 attendees and a wide range of presenters covering careers in academia, research-industry collaboration, innovative bio-research activity and much much more,” said Annemarie Nadort.

“There was so much positive feedback from participants on the day and we’ve kick-started a great many conversations and discussions which will hopefully build new research relationships and lead to even more innovative science taking place.”

Below – Organiser Annemarie Nadort observing the successful symposium panel discussion from the wings.

Understanding the role that sugars play

30 March 2018:

CNBP scientists Chris Ashwood (pictured) and Prof Nicki Packer at Macquarie University have shown that sugars with exactly the same chemical composition but slightly different structure break apart differently in their latest publication in the area of mass spectrometry. This work is their first step in automating sugar analysis, to understand the role sugars play in human disease.

Journal: Journal of The American Society for Mass Spectrometry.

Publication title: Discrimination of Isomers of Released N- and O-Glycans Using Diagnostic Product Ions in Negative Ion PGC-LC-ESI-MS/MS.

Authors: Christopher Ashwood, Chi-Hung Lin, Morten Thaysen-Andersen, Nicolle H. Packer.

Abstract:
Profiling cellular protein glycosylation is challenging due to the presence of highly similar glycan structures that play diverse roles in cellular physiology. As the anomericity and the exact linkage type of a single glycosidic bond can influence glycan function, there is a demand for improved and automated methods to confirm detailed structural features and to discriminate between structurally similar isomers, overcoming a significant bottleneck in the analysis of data generated by glycomics experiments. We used porous graphitized carbon-LC-ESI-MS/MS to separate and detect released N- and O-glycan isomers from mammalian model glycoproteins using negative mode resonance activation CID-MS/MS. By interrogating similar fragment spectra from closely related glycan isomers that differ only in arm position and sialyl linkage, product fragment ions for discrimination between these features were discovered. Using the Skyline software, at least two diagnostic fragment ions of high specificity were validated for automated discrimination of sialylation and arm position in N-glycan structures, and sialylation in O-glycan structures, complementing existing structural diagnostic ions. These diagnostic ions were shown to be useful for isomer discrimination using both linear and 3D ion trap mass spectrometers when analyzing complex glycan mixtures from cell lysates. Skyline was found to serve as a useful tool for automated assessment of glycan isomer discrimination. This platform-independent workflow can potentially be extended to automate the characterization and quantitation of other challenging glycan isomers.

CINSW Fellowship awarded

16 March 2018:

It has been formally announced that Dr Andrew Care, former CNBP Research Fellow and now Centre Associate Investigator, has been awarded a 2018 Early Career Fellowship from the Cancer Institute New South Wales (CINSW) to fund the research project, ‘Biological nanoparticles for the targeted delivery and light-triggered release of drugs’.

This project aims to develop novel protein nanocages for the targeted co-delivery and controlled release of therapeutics in the multimodal treatment of cancer.

In addition, PhD Candidate Ms Dennis Diaz, who is part of the team working on this exciting project, was recently awarded a Research Scholarship Award from the translational cancer research centre, Sydney Vital.

Dennis is working under the supervision of Dr Andrew Care and A/Prof. Anwar Sunna (also a CNBP Associate Investigator).

Further information on the CINSW and its recent grants announcement is available here.