Louis Rendina

Gadolinium theranostics for the diagnosis and treatment of cancer

Publisher: Royal Society of Chemistry (RSC)

Date: 2021

DOI: 10.1039/D0CS01075H

Abstract: Combining therapeutic and diagnostic tools into a single ‘theranostic’ platform lies at the forefront of cancer research. Some of the most promising theranostics exploit the unique nuclear and electronic properties of the lanthanoid metal gadolinium.

Carborane clusters increase the potency of bis-substituted cyclam derivatives against Mycobacterium tuberculosis

Publisher: Royal Society of Chemistry (RSC)

Date: 2022

DOI: 10.1039/D2MD00150K

Abstract: Bis-substituted cyclam derivatives have recently emerged as a promising new class of antibacterial agents, displaying excellent activity against drug-resistant Mycobacterium tuberculosis ( Mtb ). Carborane pendants enhance this activity.

Selective delivery of remarkably high levels of gadolinium to tumour cells using an arsonium salt

Publisher: Royal Society of Chemistry (RSC)

Date: 2021

DOI: 10.1039/D1CC03082E

Abstract: A triphenylarsonium targeting vector is far superior to the well-established, isosteric phosphonium analogue for tumour cell delivery of Gd 3+ .

A novel Arabidopsis-oomycete pathosystem: differential interactions withPhytophthora capsicireveal a role for camalexin, indole glucosinolates and salicylic acid in defence

Publisher: Wiley

Date: 10-01-2013

DOI: 10.1111/PCE.12052

Abstract: Phytophthora capsici causes devastating diseases on a broad range of plant species. To better understand the interaction with its host plants, knowledge obtained from a model pathosystem can be instrumental. Here, we describe the interaction between P. capsici and Arabidopsis and the exploitation of this novel pathosystem to assign metabolic pathways involved in defence against P. capsici. Inoculation assays on Arabidopsis accessions with different P. capsici isolates revealed interaction specificity among accession-isolate combinations. In a compatible interaction, appressorium-mediated penetration was followed by the formation of invasive hyphae, haustoria and sporangia in leaves and roots. In contrast, in an incompatible interaction, P. capsici infection elicited callose deposition, accumulation of active oxygen species and cell death, resulting in early pathogen encasement in leaves. Moreover, Arabidopsis mutants with defects in salicylic acid signalling, camalexin or indole glucosinolates biosynthesis pathways displayed severely compromised resistance to P. capsici. It is anticipated that this model pathosystem will facilitate the genetic dissection of complex traits responsible for resistance against P. capsici.

Histone Deacetylase 2 (HDAC2) Inhibitors Containing Boron

Publisher: Wiley

Date: 16-06-2020

DOI: 10.1002/CBIC.202000131

Abstract: Histone deacetylase enzymes (HDACs) are responsible for the global silencing of tumour‐suppressor genes. Treatment with a histone deacetylase inhibitor (HDACi) can reverse this process and restore normal cell function. Herein, we report a small series of boron‐based (boronic acid, boronate ester and closo‐ 1,2‐carborane) HDAC2 inhibitors with IC 50 values in the nanomolar range. The boronate ester 4 b was the most potent compound assessed in this study (IC 50 =40.6±1.5 nM), followed closely by the 1,2‐ closo ‐carborane (IC 50 =42.9±1.5 nM). Compound 4 b exceeds the potency of the related gold‐standard HDAC pan‐inhibitor vorinostat ( 1 ) toward this particular HDAC isoform.

New boron-based coumarin fluorophores for bioimaging applications

Publisher: CSIRO Publishing

Date: 29-03-2022

DOI: 10.1071/CH21320

Abstract: The synthesis and characterisation of five new boron-based coumarin fluorophores are reported, with key structural variations involving the linker at the C3-position (hydrazone or imine) of the 7-(diethylamino)-coumarin (7DEAC) core and the terminal boron moiety (i.e. boronic acid or closo-1,2-carborane). All the coumarin derivatives were found to display significant bathochromic shifts relative to the parent 7DEAC, with conjugate ICCb displaying the greatest overall shift. Confocal microscopy studies with A549 lung cancer cells showed clear differences in the observed intra-cellular distributions of the fluorophores. The polar boronic acid species (HCoBA, HCmBA and HCpBA) were found to localise in the endoplasmic reticulum. In contrast, the lipophilic closo-1,2-carborane derivatives (HCCb and ICCb) were found to localise within lipid droplets (LDs), showcasing the future potential for these probes to be utilised as stains for LD observations by means of confocal microscopy.

Significant cell uptake of Gd(iii)-diphenylphosphoryl-diphenylphosphonium complexes: evidence for a new conformationally-dependent tumour cell targeting vector

Publisher: Royal Society of Chemistry (RSC)

Date: 2023

DOI: 10.1039/D3CC02706F

Induced expression of defense-related genes inArabidopsisupon infection withPhytophthora capsici

Publisher: Informa UK Limited

Date: 07-2013

DOI: 10.4161/PSB.24618

Phenotypic Analyses of Arabidopsis T-DNA Insertion Lines and Expression Profiling Reveal That Multiple L-Type Lectin Receptor Kinases Are Involved in Plant Immunity

Publisher: Scientific Societies

Date: 12-2014

DOI: 10.1094/MPMI-06-14-0191-R

Abstract: L-type lectin receptor kinases (LecRK) are membrane-spanning receptor-like kinases with putative roles in biotic and abiotic stress responses and in plant development. In Arabidopsis, 45 LecRK were identified but their functions are largely unknown. Here, a systematic functional analysis was carried out by evaluating phenotypic changes of Arabidopsis LecRK T-DNA insertion lines in plant development and upon exposure to various external stimuli. None of the LecRK T-DNA insertion lines showed clear developmental changes, either under normal conditions or upon abiotic stress treatment. However, many of the T-DNA insertion lines showed altered resistance to Phytophthora brassicae, Phytophthora capsici, Pseudomonas syringae, or Alternaria brassicicola. One mutant defective in LecRK-V.5 expression was compromised in resistance to two Phytophthora spp. but showed enhanced resistance to Pseudomonas syringae. LecRK-V.5 overexpression confirmed its dual role in resistance and susceptibility depending on the pathogen. Combined analysis of these phenotypic data and LecRK expression profiles retrieved from public datasets revealed that LecRK which are hardly induced upon infection or even suppressed are also involved in pathogen resistance. Computed coexpression analysis revealed that LecRK with similar function displayed erse expression patterns. Because LecRK are widespread in plants, the results presented here provide invaluable information for exploring the potential of LecRK as novel sources of resistance in crops.

Carboranes in drug discovery, chemical biology and molecular imaging

Publisher: Springer Science and Business Media LLC

Date: 23-06-2022

DOI: 10.1038/S41570-022-00400-X

Arabidopsis Lectin Receptor Kinases LecRK-IX.1 and LecRK-IX.2 Are Functional Analogs in Regulating Phytophthora Resistance and Plant Cell Death

Publisher: Scientific Societies

Date: 09-2015

DOI: 10.1094/MPMI-02-15-0025-R

Abstract: L-type lectin receptor kinases (LecRK) are potential immune receptors. Here, we characterized two closely-related Arabidopsis LecRK, LecRK-IX.1 and LecRK-IX.2, of which T-DNA insertion mutants showed compromised resistance to Phytophthora brassicae and Phytophthora capsici, with double mutants showing additive susceptibility. Overexpression of LecRK-IX.1 or LecRK-IX.2 in Arabidopsis and transient expression in Nicotiana benthamiana increased Phytophthora resistance but also induced cell death. Phytophthora resistance required both the lectin domain and kinase activity, but for cell death, the lectin domain was not needed. Silencing of the two closely related mitogen-activated protein kinase genes NbSIPK and NbNTF4 in N. benthamiana completely abolished LecRK-IX.1-induced cell death but not Phytophthora resistance. Liquid chromatography-mass spectrometry analysis of protein complexes coimmunoprecipitated in planta with LecRK-IX.1 or LecRK-IX.2 as bait, resulted in the identification of the N. benthamiana ABC transporter NbPDR1 as a potential interactor of both LecRK. The closest homolog of NbPDR1 in Arabidopsis is ABCG40, and coimmunoprecipitation experiments showed that ABCG40 associates with LecRK-IX.1 and LecRK-IX.2 in planta. Similar to the LecRK mutants, ABCG40 mutants showed compromised Phytophthora resistance. This study shows that LecRK-IX.1 and LecRK-IX.2 are Phytophthora resistance components that function independent of each other and independent of the cell-death phenotype. They both interact with the same ABC transporter, suggesting that they exploit similar signal transduction pathways.

Remarkable Enhancement in Boron Uptake Within Glioblastoma Cells With Carboranyl–Indole Carboxamides

Publisher: Wiley

Date: 17-10-2018

DOI: 10.1002/ASIA.201801175

Abstract: Novel boron-rich, carboranyl-indole carboxamide ligands were prepared and found to effectively target the 18 kDa translocator protein (TSPO), an upregulated mitochondrial membrane-bound protein which has been observed in variety of tumor cell lines and its expression appears to be proportional to the degree of tumorigenicity, emphasizing a key role in cancer cell proliferation. Both boronated compounds displayed remarkably high affinities for the TSPO. In addition, the in vitro uptake of these compounds into T98G human glioma cells was found to be 25- to 100-fold greater than that of clinical boron neutron capture therapy (BNCT) agents.

Cutting edge rare earth radiometals: prospects for cancer theranostics

Publisher: Springer Science and Business Media LLC

Date: 26-08-2022

DOI: 10.1186/S41181-022-00173-0

Abstract: With recent advances in novel approaches to cancer therapy and imaging, the application of theranostic techniques in personalised medicine has emerged as a very promising avenue of research inquiry in recent years. Interest has been directed towards the theranostic potential of Rare Earth radiometals due to their closely related chemical properties which allow for their facile and interchangeable incorporation into identical bifunctional chelators or targeting biomolecules for use in a erse range of cancer imaging and therapeutic applications without additional modification, i.e. a “one-size-fits-all” approach. This review will focus on recent progress and innovations in the area of Rare Earth radionuclides for theranostic applications by providing a detailed snapshot of their current state of production by means of nuclear reactions, subsequent promising theranostic capabilities in the clinic, as well as a discussion of factors that have impacted upon their progress through the theranostic drug development pipeline. In light of this interest, a great deal of research has also been focussed towards certain under-utilised Rare Earth radionuclides with erse and favourable decay characteristics which span the broad spectrum of most cancer imaging and therapeutic applications, with potential nuclides suitable for α -therapy ( 149 Tb), β − -therapy ( 47 Sc, 161 Tb, 166 Ho, 153 Sm, 169 Er, 149 Pm, 143 Pr, 170 Tm), Auger electron (AE) therapy ( 161 Tb, 135 La, 165 Er), positron emission tomography ( 43 Sc, 44 Sc, 149 Tb, 152 Tb, 132 La, 133 La), and single photon emission computed tomography ( 47 Sc, 155 Tb, 152 Tb, 161 Tb, 166 Ho, 153 Sm, 149 Pm, 170 Tm). For a number of the aforementioned radionuclides, their progression from ‘bench to bedside’ has been hamstrung by lack of availability due to production and purification methods requiring further optimisation. In order to exploit the potential of these radionuclides, reliable and economical production and purification methods that provide the desired radionuclides in high yield and purity are required. With more reactors around the world being decommissioned in future, solutions to radionuclide production issues will likely be found in a greater focus on linear accelerator and cyclotron infrastructure and production methods, as well as mass separation methods. Recent progress towards the optimisation of these and other radionuclide production and purification methods has increased the feasibility of utilising Rare Earth radiometals in both preclinical and clinical settings, thereby placing them at the forefront of radiometals research for cancer theranostics.

University Of Sydney

Location: Australia

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University Of Utrecht, Institute Of Environmental Biology

Location: Netherlands

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Wageningen University

Location: Netherlands

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Wageningen University

Location: No location found

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Discovery Projects - Grant ID: DP0986055

Start Date: 07-2009

End Date: 12-2012

Amount: $410,000.00

Funder: Australian Research Council

Discovery Projects - Grant ID: DP120100958

Start Date: 04-2012

End Date: 12-2014

Amount: $390,000.00

Funder: Australian Research Council

Discovery Projects - Grant ID: DP190103461

Start Date: 10-2019

End Date: 12-2024

Amount: $420,000.00

Funder: Australian Research Council

Discovery Projects - Grant ID: DP0557235

Start Date: 01-2005

End Date: 12-2008

Amount: $510,000.00

Funder: Australian Research Council

Discovery Projects - Grant ID: DP110104237

Start Date: 03-2011

End Date: 03-2015

Amount: $420,000.00

Funder: Australian Research Council

Discovery Projects - Grant ID: DP0557118

Start Date: 02-2005

End Date: 11-2008

Amount: $290,000.00

Funder: Australian Research Council

Special Research Initiatives - Grant ID: SR0354474

Start Date: 01-2004

End Date: 12-2004

Amount: $30,000.00

Funder: Australian Research Council

Linkage Infrastructure, Equipment And Facilities - Grant ID: LE100100118

Start Date: 03-2011

End Date: 12-2011

Amount: $600,000.00

Funder: Australian Research Council

Linkage Infrastructure, Equipment And Facilities - Grant ID: LE140100149

Start Date: 12-2014

End Date: 06-2015

Amount: $300,000.00

Funder: Australian Research Council

Industrial Transformation Training Centres - Grant ID: IC230100046

Start Date: 2023

End Date: 12-2027

Amount: $5,000,000.00

Funder: Australian Research Council

Linkage Infrastructure, Equipment And Facilities - Grant ID: LE200100136

Start Date: 09-2020

End Date: 04-2024

Amount: $1,100,000.00

Funder: Australian Research Council