Tag Archives: Wei Deng

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.

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.

 

Light-triggerable liposomes

21 April 2017:

A new paper from CNBP researchers (lead author Wenjie Chen pictured) reports on the design of a new light-triggerable liposome. The work has just been published in the journal ‘Molecular Therapy: Nucleic Acid’ and is accessible online.

Journal: Molecular Therapy: Nucleic Acid.

Title: Light-triggerable liposomes for enhanced endo/lysosomal escape and gene silencing in PC12 cells.

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

Abstract: Liposomes are an effective gene/drug delivery system, widely used in biomedical applications including gene therapy and chemotherapy. Here we designed a photo-responsive liposome (lipVP) loaded with a photosensitizer verteporfin (VP). This photosensitizer is clinically approved for photodynamic therapy (PDT). LipVP was employed as a DNA carrier for pituitary adenylyl cyclase-activating polypeptide (PACAP) receptor 1 (PAC1R) gene knockdown in PC12 cells. This has been done by incorporating PAC1R antisense oligonucleotides inside the lipVP cavity. Cells which have taken up the lipVP were exposed to light from a UV light source. As a result of this exposure, reactive oxygen species (ROS) were generated from VP, destabilising the endo/lysosomal membranes and enhancing the liposomal release of antisense DNA into the cytoplasm. Endo/lysosomal escape of DNA was documented at different time points based on quantitative analysis of colocalization between fluorescently labelled DNA and endo/lysosomes. The released antisense oligonucleotides were found to silence PAC1R mRNA. The efficiency of this photo-induced gene silencing was demonstrated by a 74 ± 5% decrease in PAC1R fluorescence intensity. Following the light-induced DNA transfer into cells, cell differentiation with exposure to two kinds of PACAP peptides was observed to determine the cell phenotypic change after PAC1R gene knockdown.

Gold-loaded liposomes with photosensitizers for PDT

2 February 2017:

A new publication from CNBP researchers Wei Deng (pictured), Sandhya Clement and Ewa Goldys indicates that gold-loaded liposomes incorporating photosensitizers may serve as improved agents in photodynamic therapy and chemotherapy. The work has just been reported in the International Journal of Nanomedicine and is accessible online.

Journal: International Journal of Nanomedicine.

Title: Light-triggered liposomal cargo delivery platform incorporating photosensitizers and gold nanoparticles for enhanced singlet oxygen generation and increased cytotoxicity

Authors: Zofia Kautzka, Sandhya Clement, Ewa M Goldys and Wei Deng.

Abstract: We developed light-triggered liposomes incorporating 3–5 nm hydrophobic gold
nanoparticles and Rose Bengal (RB), a well-known photosensitizer used for photodynamic
therapy. Singlet oxygen generated by these liposomes with 532 nm light illumination was
characterized for varying the molar ratio of lipids and gold nanoparticles while keeping
the amount of RB constant. Gold nanoparticles were found to enhance the singlet oxygen
generation rate, with a maximum enhancement factor of 1.75 obtained for the molar ratio of hydrogenated soy l-α-phosphatidylcholine:1,2-dioleoyl-sn-glycero-3-hosphoethanolamineN-(hexanoylamine): gold of 57:5:17 compared with liposomes loaded with RB alone. The experimental results could be explained by the local electric field enhancement caused by gold nanoparticles. We further assessed cellular cytotoxicity of gold-loaded liposomes by encapsulating an antitumor drug, doxorubicin (Dox); such Dox-loaded liposomes were applied to human colorectal cancer cells (HCT116) and exposed to light. Gold-loaded liposomes containing RB and Dox where Dox release was triggered by light were found to exhibit higher cytotoxicity compared with the liposomes loaded with RB and Dox alone. Our results indicate that goldloaded liposomes incorporating photosensitizers may serve as improved agents in photodynamic therapy and chemotherapy.

PLGA nanocomposites developed for PDT of cancer cells

staff photos for Centre of Excellence in Nanoscale Biophotonics (CNBP)24 November 2016:

In this latest paper, CNBP researchers (lead author Wei Deng pictured left) developed PLGA nanocomposites by incorporating a photosensitizer, verteporfin and gold nanoparticles into the polymeric matrix and utilised them for enhanced photodynamic therapy of cancer cells.

Journal: RSC Advances.

Title: PLGA nanocomposites loaded with verteporfin and gold nanoparticles for enhanced photodynamic therapy of cancer cells.

Authors: Wei Deng, Zofia Kautzka, Wenjie Chen and Ewa M Goldys.

Abstract: In this paper, PLGA nanocomposites were developed by incorporating a photosensitizer, verteporfin and gold nanoparticles into the polymeric matrix and utilised for enhanced photodynamic therapy of cancer cells. Both enhanced fluorescence and O2 generation from verteporfin were observed in this new formulation under both 425 nm LED and 405 nm laser illumination. A maximum enhancement factor of 2.5 for fluorescence and 1.84 for O2 generation was obtained when the molar ratio of gold : VP was 5:1 and excited at 425 nm, compared with PLGA doped with verteporfin alone. The experiment results could be explained by the local electric field enhancement of gold nanoparticles. Furthermore, improved therapeutic efficacy in human pancreatic cancer cells, PANC-1, was also demonstrated by using this new formulation following light exposure, indicating the utility of these nanocomposites for enhanced photodynamic therapy.

The paper is accessible online.

Counting cancer-busting oxygen molecules

Ewa Goldys Low Res Edit 015928 January 2016:

CNBP researchers have established that a therapeutic dose of X-rays, in combination with CeF3 nanoparticles, can produce enough singlet oxygen molecules to be effective in photodynamic therapy. The finding has been reported in the journal Scientific Reports, published online today.

The complete research paper is available for download, from the Nature Publishing Group web site. A CNBP media release has also been produced.

Nanoparticles, velcro, marbles and a hot glue gun

CNBPat Questacon SciComm event Dec 2014-2

16 December 2014 :Science Communication workshop.
“If you can’t explain it simply, you don’t understand it well enough.” – Albert Einstein.

On December 15-16th, 9 CNBP ECRs from University of Adelaide,  RMIT University, Macquarie University and SAHMRI attended a science communication workshop at the Questacon workshop (Canberra) and were taught the importance of translating their research into lay terms. More specifically, explaining concepts such as the use of nanoparticles for targeted drug therapy to an 8 year old. Its harder than you think and involves the art of scaffolding; i.e. simplifying a concept by using analogies.

The most interactive and fun session of the workshop involved us creating models and physical demonstrations of our research and included us all running around the Questacon workshop to explain current, throwing paper at people as a demonstration of drug delivery, different coloured glow sticks as an analogy for the use of nanoparticles/probes to diagnose pain and the use of lots and lots of velcro and hot glue guns to make “up-scaled” nanoparticles. Think Playschool for scientists.

CNBP were proud to be sponsors of this professional development workshop which was developed by The ARC Centre of Excellence for Electromaterials Science, in partnership with the ARC Centre of Excellence in Convergent Bio-Nano Science and Technology and the ARC Centre of Excellence in Nanoscale BioPhotonics.

The workshop was designed to teach participants how to put their best foot forward in media interviews, community talks and scientific presentations.

CNBP-themed Research Conference at Macquarie University

Andrei and Igor12 December 2014: They just could not stop talking!

Finishing 2014 on a high note the Macquarie CNBP node organized a CNBP-themed  MQ BioFocus Research Conference on 10 December.

An ECR-led Conference Committee comprising Dr Wei Deng, Ms K. Drozdowicz-Tomsia, and Dr Varun Sreenivasan put together an exciting program of talks and posters, covering disciplines from medicine to laser physics.

Rarely have we seen more lively discussions!

The meeting was attended by 70 staff and students from CNBP and Macquarie MQ BioFocus Research Centre led by Professor Ewa Goldys (Deputy Director, CNBP).

CNBP Associate Investigators (pictured above) A/Prof Igor Aharonovich (right) and Andrei Zvyagin (left) have presented their research.

MQ BioFocus Research Centre was established in 2010 and it laid the foundation for the CNBP node at Macquarie.