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.
26 October 2017:
A new paper featuring CNBP researchers (lead author Sandhya Clement pictured top left), demonstrates a simple, non-destructive method suitable for rapid evaluation of nanoparticles in colloidal suspension.
The paper, published in Nanotechnology is accessible online.
Publication title: Quantification of nanoparticle concentration in colloidal suspensions by a non-destructive optical method.
Authors: Sandhya Clement, Brint Gardner, Wan Aizuddin W Razali, Victoria A Coleman, Åsa K Jämting, Heather J Catchpoole, Ewa M Goldys, Jan Herrmann and Andrei Zvyagin.
Abstract: The estimation of nanoparticle number concentration in colloidal suspensions is a prerequisite in many procedures, and in particular in multi-stage, low-yield reactions. Here, we describe a rapid, non-destructive method based on optical extinction and dynamic light scattering (DLS), which combines measurements using common bench-top instrumentation with a numerical algorithm to calculate the particle size distribution (PSD) and concentration. These quantities were derived from Mie theory applied to measurements of the optical extinction spectrum of homogeneous, non-absorbing nanoparticles, and the relative PSD of a colloidal suspension. The work presents
an approach to account for PSDs achieved by DLS which, due to the underlying model, may not be representative of the true sample PSD. The presented approach estimates the absolute particle number concentration of samples with mono-, bi-modal and broad size distributions with <50% precision. This provides a convenient and practical solution for number concentration estimation required during many applications of colloidal nanomaterials.
22 March 2017:
A new publication from CNBP researchers (lead author Sandhya Clement pictured) reports on a more effective and less harmful gold-based nano-agent for bioimaging and photodynamic therapy treatment for deep tissue tumors.
The work has just been reported in the journal ‘Microchimica Acta ’ and is accessible online.
Journal: Microchimica Acta.
Title: Verteprofin conjugated to gold nanoparticles for fluorescent cellular bioimaging and X-ray mediated photodynamic therapy.
Authors: Sandhya Clement, Wenjie Chen, Ayad G. Anwer & Ewa M. Goldys.
Abstract: Photodynamic therapy (PDT) uses photosensitizers, light and molecular oxygen to generate cytotoxic reactive oxygen species. Its effectiveness is limited to <1 cm due to the limited penetration depth of light. The present study compares the PDT effectivity of the photosensitizer verteporfin (VP) conjugated to gold nanoparticles (AuNPs) (a) by using deeply penetrating X-rays administered in standard radiotherapy doses, and (b) by using red light (690 nm). VP was conjugated to AuNPs of around 12 nm size to enhance the interaction of ionizing radiation with PS. For comparison, VP also was directly exposed to X-rays. It is found that VP alone is stimulated by X-rays to generate singlet oxygen. The conjugate to AuNPs also generated a significant amount of singlet oxygen on irradiation with X-rays in comparison to illumination with 690-nm light. It is also found that the rate of singlet oxygen generation is amplified in case of AuNP-conjugated VP compared to VP alone. The performance of the AuNP-VP conjugate and of the VP alone was tested in Panc 1 cells. Their viability was impaired much more in these two scenarios than with the X-ray radiation only. This suggests excellent perspectives for PDT based on VP and with X-ray stimulation, both as a stand-alone photosensitizer and in Au-NP conjugates. Moreover, both VP and AuNP-VP conjugates show bright fluorescence in physiological media for excitation/emission wavelengths in the range of 405/690 nm; hence they can also be used for simultaneous bioimaging.
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.
12 December 2016:
Congratulations to our recent CNBP PhD graduate, Dr Sandhya Clement who has just won a Macquarie University Faculty of Science Award for ‘Excellence in Sessional Teaching’.
Well done Sandhya!
10 August 2016:
Researchers from the CNBP have published a paper reporting on the modification of the efficiency of singlet oxygen generation in photosensitizers conjugated to dielectric (CeF3) and metal (Au) nanoparticles in water.
Journal: Journal of Photochemistry and Photobiology A: Chemistry.
Publication title: Nanoparticle-mediated singlet oxygen generation from photosensitizers.
Authors: Sandhya Clement (pictured above), Mushtaq Sobhan, Wei Deng, Elizabeth Camilleri, Ewa M. Goldys.
Abstract: We report on the modification of the efficiency of singlet oxygen generation in photosensitizers conjugated to dielectric (CeF3) and metal (Au) nanoparticles in water. The conjugates were formed with two photosensitizers, verteporfin and Rose Bengal. Quantitative analysis of the singlet oxygen generation demonstrated that the conjugation of the photosensitizer to a nanoparticle increases the efficiency of the photosensitizers to produce singlet oxygen in water. The singlet oxygen quantum yield of UV-sensitized verteporfin increases by a factor of 1.45 and 1.64 for CeF3-verteporfin and Au-verteporfin conjugates respectively compared to unconjugated verteporfin. Furthermore, Au-Rose Bengal conjugates also demonstrated enhanced singlet oxygen yield when sensitized at the plasmonic wavelength of 532 nm. We quantitatively explain these findings by the electric field enhancements around the nanoparticles.
The paper is available online.
28 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.