Browsing by Author "Westlake, M"

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    First extensive study of lanthanum manganite nanoparticles to target deadly brain cancer
    (Australian Institute of Nuclear Science and Engineering (AINSE), 2020-11-11) Khochaiche, A; Westlake, M; O'Keefe, A; Engels, E; Li, N; Vogel, S; Valceski, M; Konstantinov, K; Corde, S; Lerch, MLF; Tehei, M; Rule, KC; Horvat, J
    The ability to successfully target deep-seated tumours in sensitive areas of the body is limited to adequate targeting strategies. More specifically, brain and central nervous system (CNS) cancers can be the most aggressive, have higher mortality rates and lower accessibility to chemotherapeutic drugs. A proposed solution to target these concerns is through introducing high atomic number (Z) nanoparticles (NPs) such as silver-doped lanthanum manganite (LAGMO) to aid in common treatments such as radiation therapy. These NPs can bypass the blood brain barrier and are capable of increasing the damage from the radiation due to their high-Z. Most importantly they have potential to cause cancer cells to undergo hyperthermia (a cell death precursor) as the NPs heat up in their environment due to their Curie temperature being in the hyperthermia range of interest.
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    First extensive study of silver-doped lanthanum manganite nanoparticles for inducing selective chemotherapy and radio-toxicity enhancement
    (Elsevier B. V., 2021-04) Khochaiche, A; Westlake, M; O'Keefe, A; Engels, E; Vogel, S; Valceski, M; Li, N; Rule, KC; Horvat, J; Konstantinov, K; Rosenfeld, AB; Lerch, MLF; Corde, S; Tehei, M
    Nanoparticles have a great potential to increase the therapeutic efficiency of several cancer therapies. This research examines the potential for silver-doped lanthanum manganite nanoparticles to enhance radiation therapy to target radioresistant brain cancer cells, and their potential in combinational therapy with magnetic hyperthermia. Magnetic and structural characterisation found all dopings of nanoparticles (NPs) to be pure and single phase with an average crystallite size of approximately 15 nm for undoped NPs and 20 nm for silver doped NPs. Additionally, neutron diffraction reveals that La0.9Ag0.1MnO3 (10%-LAGMO) NPs exhibit residual ferromagnetism at 300 K that is not present in lower doped NPs studied in this work, indicating that the Curie temperature may be manipulated according to silver doping. This radiobiological study reveals a completely cancer-cell selective treatment for LaMnO3, La0.975Ag0.025MnO3 and La0.95Ag0.05MnO3 (0, 2.5 and 5%-LAGMO) and also uncovers a potent combination of undoped lanthanum manganite with orthovoltage radiation. Cell viability assays and real time imaging results indicated that a concentration of 50 μg/mL of the aforementioned nanoparticles do not affect the growth of Madin-Darby Canine Kidney (MDCK) non-cancerous cells over time, but stimulate its metabolism for overgrowth, while being highly toxic to 9L gliosarcoma (9LGS). This is not the case for 10%-LAGMO nanoparticles, which were toxic to both non-cancerous and cancer cell lines. The nanoparticles also exhibited a level of toxicity that was regulated by the overproduction of free radicals, such as reactive oxygen species, amplified when silver ions are involved. With the aid of fluorescent imaging, the drastic effects of these reactive oxygen species were visualised, where nucleus cleavage (an apoptotic indicator) was identified as a major consequence. The genotoxic response of this effect for 9LGS and MDCK due to 10%-LAGMO NPs indicates that it is also causing DNA double strand breaks within the cell nucleus. Using 125 kVp orthovoltage radiation, in combination with an appropriate amount of NP-induced cell death, identified undoped lanthanum manganite as the most ideal treatment. Real-time imaging following the combination treatment of undoped lanthanum manganite nanoparticles and radiation, highlighted a hinderance of growth for 9LGS, while MDCK growth was boosted. The clonogenic assay following incubation with undoped lanthanum manganite nanoparticles combined with a relatively low dose of radiation (2 Gy) decreased the surviving fraction to an exceptionally low (0.6 ± 6.7)%. To our knowledge, these results present the first biological in-depth analysis on silver-doped lanthanum manganite as a brain cancer selective chemotherapeutic and radiation dose enhancer and as a result will propel its first in vivo investigation. © 2021 Elsevier B.V.
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    Investigations into the controllable change of Curie temperature in silver doped lanthanum manganite nanoparticles
    (Australian Institute of Nuclear Science and Engineering, 2016-11-29) Westlake, M; Lerch, MLF; Konstantinov, K; Rule, KC; Yu, DH; Pan, AV; Cardillo, D; Horvat, J; Tehei, M
    Our team is focused on research into the design, production, characterisation and implementation of optimized nanostructured particles for principally the diagnosis (as CT and MRI contrast agents) and treatment of cancer (using radiation, oncothermia and hyperthermia modalities). One magnetic nanoparticle of current interest is Lanthanum Manganite (LaMnO3) and its silver doped counterpart (La1-xAgxMnO3). The high effective atomic number and magnetic moment of LaMnO3 [1] makes this material appropriate for the basis of an MRI and CT contrast agent and enhancing radiation therapies. In addition La1-xAgxMnO3 is also considered as a good candidate for hyperthermia cancer therapy [2].For the characterization of our samples we used XRD, PPMS, SEM, EDS and SEM. We observed that the Curie temperature increased with the increase of the silver doping concentration in the nanoparticles. This has led to an investigation into the mechanism behind this change. The spin-phonon interaction was considered to represent one potential mechanism and Time of Flight measurements where conducted on PELICAN at ANSTO. A lack of phonon evolution was seen within the temperature range of 1.5K - 300K. In order to access phonon density of states over a broader range of energies, we are then planning to use the Beryllium filter on TAIPAN and scan through a wide energy range while measuring scattered neutron over a vastly increased solid angle. The following poster will focus on the characterizations of our samples, our first experiments on PELICAN and our future planed experiments in the aim to better understand the mechanism that provokes the change of Curie temperature upon silver doping.