Category Archives: publication

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New nanoparticles help detect deep-tissue cancers

6 August 2018:

Researchers have developed a new form of nanoparticle and associated imaging technique that can detect multiple disease biomarkers, including those for breast cancer, found in deep-tissue in the body.

Reported in the science journal ‘Nature Nanotechnology’, the research opens up a new avenue in minimally invasive disease diagnosis and will potentially have widespread use both for biomedical research and for clinical applications.

“The use of nanoparticles for bio-imaging of disease is an exciting and fast-moving area of science,” says research author Dr Yiqing Lu (pictured) at the ARC Centre of Excellence for Nanoscale BioPhotonics (CNBP), Macquarie University.

“Specially designed nanoparticles can be placed in biological samples or injected into specific sites of the body and then ‘excited’ by introduced light such as that from a laser or an optical fibre,” he says.

“Disease biomarkers targeted by these nanoparticles then reveal themselves, by emitting their own specific wavelength signatures which are able to be identified and imaged.”

A major limitation however is that only a single disease biomarker at a time is able to be distinguished and quantified in the body using this type of detection technique.

“Detection of multiple biomarkers (known as multiplexing) in the body has been a major challenge for researchers,” says Dr Lu.

“The tissue environment is extremely complex—full of light absorbing and scattering elements such as blood, muscle and cartilage. And introducing multiple nanoparticles to a site, operating at multiple wavelengths to detect multiple biomarkers, produces too much interference. It makes it extremely difficult to determine accurately if a range of disease biomarkers are present.”

What Dr Lu and the research team have done to solve this issue has been to engineer innovative nanoparticles that emit light at the same frequency (near infrared light) but that are able to be coded to emit light for set periods of time (in the microsecond-to-millisecond time range).

“It is the duration of the light-emission and the biomarker reaction to this timed amount of light (known as luminescence lifetime) that produces a clearly identifiable molecular signature,” he says.

“Multiple disease biomarkers can be clearly identified and imaged based on this approach as there are no overlapping wavelengths interfering with the reading.”

“This enables high-contrast optical biomedical imaging that can detect multiple disease biomarkers all at the one time.” says Dr Lu.

In an exciting breakthrough in laboratory testing, the innovative nanoparticles have been able to detect multiple forms of breast cancer tumours in mice.

“We’re extremely excited where this work is taking us,” says Professor Fan Zhang at Fudan University (China) and joint-lead author on the research publication.

“We were able to successfully detect and identify key biomarkers for a number of different sub-types of breast cancer.”

“This technique has the potential to provide a low-invasive method of determining if breast cancer is present, as well as the form of breast cancer, without the need to take tissue samples via biopsy.”

“Ultimately our novel nanoparticles will enable quantitative assessment for a wide range of disease and cancer biomarkers, all at one time. The technique will be able to be used for early-stage disease screening and potentially utilised in integrated therapy,” says Professor Fan Zhang.

Professor Jim Piper, CNBP node leader at Macquarie University and also an author on the paper is similarly upbeat with the results that have been obtained.

“This is a major advance in a long-term effort at our Centre at Macquarie University to develop innovative techniques for simultaneous detection of multiple disease markers in humans and animals,” he says.

“Next steps in our research collaboration are to further refine the nanoparticles, to examine issues related to a clinical roll-out of the technology and to explore further applications and disease areas where this technique could be best utilised.”

Reported in the prestigious journal ‘Nature Nanotechnology’, the international team of researchers involved with the study are based at the ARC Centre of Excellence for Nanoscale BioPhotonics (CNBP), Macquarie University and Fudan University, China.

Notably, the work is an extension of previous nanoparticle-imaging research undertaken by Dr Lu at Macquarie University which has been awarded a patent in the United States and China, and which has already been licensed with commercial partners.

Journal: Nature Nanotechnology.

Publication title: Lifetime-engineered NIR-II nanoparticles unlock multiplexed in vivo imaging.

Authors: Yong Fan, Peiyuan Wang, Yiqing Lu, Rui Wang, Lei Zhou, Xianlin Zheng, Xiaomin Li, James A. Piper & Fan Zhang.

Below: A stylised image of cancer detecting nanoparticles in the body. Credit: Yong Fan.

Engineering protein-based nanoparticles

23 July 2018:

A new review paper has been published in the journal ‘Genes’ featuring two CNBP Associate Investigators as co-authors, Dr Andrew Care (Cancer Institute NSW) and Dr Anwar Sunna (Macquarie University).

Titled, ‘Bioengineering Strategies for Protein-based Nanoparticles’, the paper focuses on the tools available to custom-engineer protein-based nanoparticles for different applications, including those in nanomedicine and biotechnology.

First author of the paper, and co-supervised by Dr Care and Dr Sunna is Ms Dennis Diaz (pictured left in photo).

Journal: Genes.

Publication title: Bioengineering Strategies for Protein-Based Nanoparticles.

Authors: Dennis Diaz, Andrew Care and Anwar Sunna.

Abstract: In recent years, the practical application of protein-based nanoparticles (PNPs) has expanded rapidly into areas like drug delivery, vaccine development, and biocatalysis. PNPs possess unique features that make them attractive as potential platforms for a variety of nanobiotechnological applications. They self-assemble from multiple protein subunits into hollow monodisperse structures; they are highly stable, biocompatible, and biodegradable; and their external components and encapsulation properties can be readily manipulated by chemical or genetic strategies. Moreover, their complex and perfect symmetry have motivated researchers to mimic their properties in order to create de novo protein assemblies. This review focuses on recent advances in the bioengineering and bioconjugation of PNPs and the implementation of synthetic biology concepts to exploit and enhance PNP’s intrinsic properties and to impart them with novel functionalities.

A photoresponsive LPD system developed

19 July 2018:

CNBP researchers have published a paper reporting on  the development of a novel photoresponsive liposome-polycation-DNA (LPD) platform. Lead author on the paper was Wenjie Chen (pictured).

Journal: Journal of Materials Chemistry B.

Publication title: Photoresponsive endosomal escape enhances gene delivery using liposome-polycation-DNA (LPD) nanovector.

Authors: Wenjie Chen, Wei Deng, Xin Xu, Xiang Zhao, Jenny Nhu Vo, Ayad G. Anwer, Thomas C. Williams, Haixin Cui, Ewa M. Goldys.

Abstract: Lipid-based nanocarriers with stimuli responsiveness have been utilized as controlled release systems for gene/drug delivery applications. In our work, by taking advantage of high complexation capbility of polycations and the light triggered property, we designed a novel photoresponsive liposome-polycation-DNA (LPD) platform. This LPD carrier incorporates verteporfin (VP) in lipid bilayers and the complex of polyethylenimine (PEI)/plasmid DNA (pDNA) encoding EGFP (polyplex) in the central cavities of liposomes. The liposomes were formulated with cationic lipids, PEGylated neutral lipids and cholesterol molecules, which improve their stability and cellular uptake in the serum-containing media. We evaluated the nanocomplex stability by monitoring size changes over six days, and the celluar uptake of nanocomplex by imaging the intracellular route. We also demonstrated light triggered the cytoplasmic release of pDNA upon irradiation with a 690 nm LED light source. Furthermore this light triggered mechanism has been studied at subcellular level. The activated release is driven by the generation of reactive oxygen species (ROS) from VP after light illumination. These ROS oxidize and destabilize the liposomal and endolysosomal membranes, leading to the release of pDNA into the cytosol and subsequent gene transfer activities. Light-triggered endolysosomal escape of pDNA at different time points was confirmed by quantitative analysis of colocalization between pDNA and endolysosomes. The increased expression of the reporter EGFP in human colorectal cancer cells was also quantified after light illumination at various time points. The efficiency of this photo-induced gene transfection was demonstrated to be more than double compared to non-irradiated controls. Additionally, we observed reduced cytotoxicity of the LPDs compared with the polyplexes alone. This study have thus shown that light-triggered and biocompatible LPDs enable improved control of efficient gene delivery which will be beneficial for future gene therapies.

X-ray triggered nano-bubbles to target cancer

13 July 2018:

Innovative drug filled nano-bubbles, able to be successfully triggered in the body by X-rays, have been developed by CNBP and Macquarie University researchers, paving the way for a new range of cancer treatments for patients.

The tiny bubbles, known as liposomes, are commonly used in pharmacology to encapsulate drugs, making them more effective in the treatment of disease. Researchers have now been able to engineer these liposomes to discharge their drug cargo on-demand, once activated by standard X-rays. Initial testing has shown this technique to be highly efficient in killing bowel cancer cells.

“The development and application of various nanomaterial designs for drug delivery is currently a key focus area in nanomedicine,” says lead author of the research Dr Wei Deng (pictured), Associate Investigator at the ARC Centre of Excellence for Nanoscale BioPhotonics (CNBP) and scientist at Macquarie University when the research was undertaken.

“Liposomes are already well established as an extremely effective drug-delivery system. Made out of similar material as cell membranes, these ‘bubbles’ are relatively simple to prepare, can be filled with appropriate medications and then injected into specific parts of the body. The issue however, is in controlling the timely release of the drug from the liposome,” she says.

“We have ensured that the liposomes release their drug pay-load at exactly the right time and in exactly the right place to ensure the most effective treatment. One way of doing this is to trigger the collapse of the liposome when and where it is needed. Our X-ray triggerable liposomes allow this on-demand drug-release to occur,” says Dr Wei Deng.

“The approach we took was to embed gold nanoparticles and the photo-sensitive molecule verteporfin into the wall of the liposome.”

“The radiation from the X-ray causes the verteporfin to react and to produce highly reactive singlet oxygen which then destabilises the liposomal membrane, causing the release of the drug,” says Dr Wei Deng.

“The gold nanoparticles are added into the mix as they focus the X-ray energy. This enhances the singlet oxygen generation and hence improves the speed of the membrane breakup”, she says.

Read the full media release here.

Journal: Nature Communications.

Publication title: Controlled gene and drug release from a liposomal delivery platform triggered by X-ray radiation.

Authors: Wei Deng, Wenjie Chen, Sandhya Clement, Anna Guller, Zhenjun Zhao, Alexander Engel & Ewa M. Goldys.

Below – Dr Wei Deng.

Vitamin D no defence against dementia

10 July 2018:

New research from South Australian scientists has shown that vitamin D (also commonly known as the sunshine vitamin) is unlikely to protect individuals from multiple sclerosis, Parkinson’s disease, Alzheimer’s disease or other brain-related disorders.

The findings, released today in the science journal ‘Nutritional Neuroscience’ reported that researchers had failed to find solid clinical evidence for vitamin D as a protective neurological agent.

“Our work counters an emerging belief held in some quarters suggesting that higher levels of vitamin D can impact positively on brain health,” says lead author Krystal Iacopetta (pictured), PhD candidate at the University of Adelaide.

“The results of our in-depth review and an analysis of all the scientific literature indicates that  there is no convincing evidence supporting vitamin D as a protective agent for the brain,” she says.

Mark Hutchinson, Director of the ARC Centre of Excellence for Nanoscale BioPhotonics (CNBP) and Professor at the University of Adelaide worked with Ms Iacopetta on the research and findings.

“This outcome is important and is based on an extremely comprehensive review and analysis of current data and relevant scientific publications,” Professor Hutchinson says.

“We’ve broken a commonly held belief that vitamin D resulting from sun exposure is good for your brain.”

Interestingly, Professor Hutchinson notes that there may be evidence that UV light (sun exposure) could impact the brain beneficially, in ways other than that related to levels of vitamin D.

“There are some early studies that suggest that UV exposure could have a positive impact on some neurological disorders such as multiple sclerosis,” he says. “We have presented critical evidence that UV light may impact molecular processes in the brain in a manner that has absolutely nothing to do with vitamin D.”

“We need to complete far more research in this area to fully understand what’s happening,” says Professor Hutchinson.

Read the full media release here.

Journal: Nutritional Neuroscience.

Publication title: Are the protective benefits of vitamin D in neurodegenerative disease dependent on route of administration? A systematic review.

Authors: Krystal Iacopetta, Lyndsey E. Collins-Praino, Femke T. A. Buisman-Pijlman, Jiajun Liu, Amanda D. Hutchinson & Mark R. Hutchinson.

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.

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.


Fluorescence microscopy gets the BAMM treatment!

7 June 2018:

A novel technique developed by researchers at the ARC Centre of Excellence for Nanoscale BioPhotonics (CNBP) will help shine new light on biological questions by improving the quality and quantity of information that can be extracted in fluorescence microscopy.

The technique, ‘bleaching-assisted multichannel microscopy’ (BAMM) takes a current long-standing weakness of fluorescence microscopy – photobleaching – and turns it into a strength that improves imaging output by up to three times, with no additional hardware required.

Reported in the journal ‘Biomedical Optics Express’ (lead author Dr Antony Orth, CNBP Research Fellow at RMIT University), BAMM will help researchers gain biological insights into the intricate processes taking place within living cells. This includes the interplay between proteins and molecules which have the potential to impact a wide range of health areas from fertility, to pain, to heart disease and more.

Publication authors: Antony Orth, Richik N. Ghosh, Emma R. Wilson, Timothy Doughney, Hannah Brown, Philipp Reineck, Jeremy G. Thompson, and Brant C. Gibson.

Read more about this innovative technique from our media release or access the publication online.

Below – This figure shows the information-rich cellular images made possible by using the newly reported BAMM technique. The ‘Original’ image shows cells containing multiple fluorescent targets, all having similar colours. This results in a monochrome image. With BAMM, photobleaching rates are colour coded red, green and blue for visualisation, so that each fluorescently labelled structure can be identified even though the fluorophore’s native colour information was never used.

Detecting glycosylated hemoglobin

Jagjit Kaur7 June 2018:

A new review paper from CNBP researchers (lead author PhD student Jagjit Kaur) outlines current research activities on developing assays including biosensors for the detection of  glycosylated hemoglobin  (HbA1c). Measurement of HbA1c is used for assessing long term glycemic control in individuals with diabetes.

Journal: Biosensors and Bioelectronics.

Publication title: Different strategies for detection of HbA1c emphasizing on biosensors and point-of-care analyzers.

Authors: Jagjit Kaur, Cheng Jiang, Guozhen Liu.

Abstract: Measurement of glycosylated hemoglobin (HbA1c) is a gold standard procedure for assessing long term glycemic control in individuals with diabetes mellitus as it gives the stable and reliable value of blood glucose levels for a period of 90–120 days. HbA1c is formed by the non-enzymatic glycation of terminal valine of hemoglobin. The analysis of HbA1c tends to be complicated because there are more than 300 different assay methods for measuring HbA1c which leads to variations in reported values from same samples. Therefore, standardization of detection methods is recommended. The review outlines the current research activities on developing assays including biosensors for the detection of HbA1c. The pros and cons of different techniques for measuring HbA1c are outlined. The performance of current point-of-care HbA1c analyzers available on the market are also compared and discussed. The future perspectives for HbA1c detection and diabetes management are proposed.

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.

A novel, high sensitivity Sagnac-interferometer biosensor

30 April 2018:

A new publication featuring CNBP co-authors (Dr Stephen Warren-Smith pictured left and Prof Heike Ebendorff-Heidepriem) reports on the design and implementation of a novel, high sensitivity Sagnac-interferometer biosensor based on an exposed core microstructured optical fiber (ECF).

Journal: Sensors and Actuators B: Chemical.

Publication title: High-sensitivity Sagnac-interferometer biosensor based on exposed core microstructured optical fiber.

Authors: Xuegang Li, Linh V. Nguyen, Yong Zhao, Heike Ebendorff-Heidepriem, Stephen C. Warren-Smith.

Abstract: A novel, high sensitivity Sagnac-interferometer biosensor based on exposed core microstructured optical fiber (ECF) has been designed and implemented in this paper. The exposed core fiber has noncircular symmetry and thus exhibits birefringence and can form a sensing element within a Sagnac loop interferometer. The exposed-core fiber design provides direct access to the evanescent field, allowing the measurement of bulk refractive index (RI) with a sensitivity of up to −3137 nm/RIU while maintaining the fiber’s robustness. The sensor can also detect the localized refractive index changes at the fiber core’s surface as the result of a biological binding event. We demonstrate the use of this sensor for label-free sensing of biological molecules by immobilizing biotin onto the fiber core as the probe to capture the target molecule streptavidin.