30 January 2017:
CNBP researchers at Macquarie University – Research Fellow Lindsay Parker (pictured left) and A/Prof Andrei Zvyagin have been successful as Chief Investigators on a $100,000 Macquarie University Research Infrastructure Block Grant.
The grant will support a research assistant (Anna Guller, CNBP PhD candidate) to help build capacity in and use Macquarie University’s bioreactor equipment towards the production and maintenance of live bioartificial tissues for sustainable scientific use.
The CNBP researchers will be collaborating with the University’s Faculty of Medicine to use these artificial biotissues in order to assess nanoparticle detection capabilities/depths in complex tissue structures.
Lead CI on the grant is Professor Qian Yi in the Faculty of Medicine.
4 January 2017:
CNBP researchers (Liuen Liang pictured), report on the deployment of upconversion nanoparticles to enhance the treatment depth of the fluorescent protein KillerRed in photodynamic therapy.
The work was published in the journal ‘Acta Biomaterialia’ and is accessible online.
Journal: Acta Biomaterialia.
Title: Deep-penetrating photodynamic therapy with KillerRed mediated by upconversion nanoparticles.
Authors: Liuen Liang, Yiqing Lu, Run Zhang, Andrew Care, Tiago A. Orteg, Sergey M. Deyev, Yi Qian, Andrei V. Zvyagina.
Abstract: The fluorescent protein KillerRed, a new type of biological photosensitizer, is considered as a promising substitute for current synthetic photosensitizes used in photodynamic therapy (PDT). However, broad application of this photosensitiser in treating deep-seated lesions is challenging due to the limited tissue penetration of the excitation light with the wavelength falling in the visible spectral range. To overcome this challenge, we employ upconversion nanoparticles (UCNPs) that are able to convert deep-penetrating near infrared (NIR) light to green light to excite KillerRed locally, followed by the generation of reactive oxygen species (ROS) to kill tumour cells under centimetre-thick tissue. The photosensitizing bio-nanohybrids, KillerRed-UCNPs, are fabricated through covalent conjugation of KillerRed and UCNPs. The resulting KillerRed-UCNPs exhibit excellent colloidal stability in biological buffers and low cytotoxicity in the dark. Cross-comparison between the conventional KillerRed and UCNP-mediated KillerRed PDT demonstrated superiority of KillerRed-UCNPs photosensitizing by NIR irradiation, manifested by the fact that ∼70% PDT efficacy was achieved at 1-cm tissue depth, whereas that of the conventional KillerRed dropped to ∼7%.
29 March 2016:
A/Prof Andrei Zvyagin, CNBP Associate Investigator located at Macquarie University, is co-author on the following nanoparticle focused paper, published in the journal ‘RSC Advances’.
Paper title: Cytotoxic effects of upconversion nanoparticles in primary hippocampal cultures.
Paper authors: Maria V Vedunova, Tatiana A Mishchenko, Elena V Mitroshina, Natalia V Ponomareva, Andrei V Yudintsev, Alla N Generalova, Sergey M Deyev, Irina V Mukhina, Alexey V Semyanov and Andrei V Zvyagin.
Abstract: The widespread use of nanomaterials causes public concerns associated with their potential toxicological hazards. New-generation nanomaterials – upconversion nanoparticles (UCNPs) – hold promise for theranostics applications due to their unique optical properties, enabling imaging at the sub-centimetre depth in live biological tissue. In brain tissue, nanoparticle-aided optical imaging and treatment are deemed desirable. To this aim, we carried out cytotoxicity studies of UCNPs in primary hippocampal cultures. The most common core/shell UCNPs (NaYF4:Yb3+:Tm3+/NaYF4) were synthesized using
a solvothermal method and hydrophilized with amphiphilic polymaleic anhydride Octadecene (PMAO); polyethyleneimine (PEI). Bare UCNPs were produced by using tetramethyl ammonium hydroxide (TMAH). PMAO-, PEI- and TMAH-UCNPs (0.8 mg mL 1) were incubated for 72 hours with primary hippocampal culture and exhibited noticeable cytotoxicity. Our studies showed profound morphological modification of all treated cells with the maximum and minimum uptake observed in PMAO- and TMAH-UCNPtreated
cells, respectively. The spontaneous calcium activity in cells treated with TMAH-UCNP, PMAOUCNP dropped to (17 3)%, (6 3)% of its original level and was completely inhibited in the PEI-UCNP treated cultures. This study demonstrated that bare and polymer surface-coated upconversion nanoparticles are toxic to dissociated hippocampal cells, evident through aberrant morphological changes, deviant variations of Ca2+ activity, and cell death.
The paper can be accessed online.