AQIRF Research Fellow
Overview
Dr Nicholas Fletcher is a research-focused academic driving studies in the radiobiology and radiopharmaceutical development space. He is based within the Centre for Advanced Imaging (CAI) at the Australian Institute for Bioengineering and Nanotechnology (AIBN) where he is the Radiobiology Theme Leader. He was awarded a 2023 Advance Queensland Industry Research Fellowship to support his projects focussed on understanding biological impacts and immunological responses to radiopharmaceuticals in collaboration with his industry partner Advancell.
Dr Fletcher and his growing team work across a range of projects, from devising and producing novel nanomedicines and targeting approaches for nanomedicines through to advanced molecular imaging approaches to probe biological responses to therapeutic interventions at unprecedented scale. To support this, he has worked to establish the Radiobiology Facility at the CAI, bringing together a nationally unique facility with capabilities that sit within only a handful of locations globally. This has enables him and his team to probe nuanced biological responses using approaches simply untenable elsewhere.
He has recent funding successes in ARC Linkage Grants so support ongoing research programs and works alongside the ARC Research Hub for Advanced Manufacture of Targeted Radiopharmaceuticals.
Research Impacts
Dr Fletcher’s research spans both traditional academic research outputs and collaborative industry programs. To date this has resulted in >60 publications, >25 industry contracts and his translational work has laid the foundation for the initiation of 3 clinical trials.
Qualifications
- Doctor of Philosophy, The University of Queensland
- Bachelor, The University of Queensland
Publications
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Forgham, Helen, Zhu, Jiayuan, Huang, Xumin, Zhang, Cheng, Biggs, Heather, Liu, Liwei, Wang, Yi Cheng, Fletcher, Nicholas, Humphries, James, Cowin, Gary, Mardon, Karine, Kavallaris, Maria, Thurecht, Kristofer, Davis, Thomas P. and Qiao, Ruirui (2024). Multifunctional Fluoropolymer‐Engineered Magnetic Nanoparticles to Facilitate Blood‐Brain Barrier Penetration and Effective Gene Silencing in Medulloblastoma. Advanced Science, e2401340. doi: 10.1002/advs.202401340
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Journal Article: A first-in-class dual-chelator theranostic agent designed for use with imaging-therapy radiometal pairs of different elements
Wood, James Liam, Ghosh, Saikat, Houston, Zachary, Fletcher, Nicholas, Humphries, James, Mardon, Karine, Akhter, Dewan T., Tieu, William, Ivashkevich, Alesia, Wheatcroft, Michael P., Thurecht, Kristofer J. and Codd, Rachel (2024). A first-in-class dual-chelator theranostic agent designed for use with imaging-therapy radiometal pairs of different elements. Chemical Science. doi: 10.1039/d4sc02851a
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Journal Article: Comparison of the hydrophilicity of water-soluble poly(2-alkyl-2-oxazoline)s, poly(2-alkyl-2-oxazine)s and poly(2,4-dialkyl-2-oxazoline)s
Mint, Kelly, Morrow, Joshua P., Warne, Nicole M., He, Xie, Pizzi, David, Shah, Shaffiq Zainal Osman, Pierens, Gregory K., Fletcher, Nicholas L., Bell, Craig A., Thurecht, Kristofer J. and Kempe, Kristian (2024). Comparison of the hydrophilicity of water-soluble poly(2-alkyl-2-oxazoline)s, poly(2-alkyl-2-oxazine)s and poly(2,4-dialkyl-2-oxazoline)s. Polymer Chemistry. doi: 10.1039/d4py00332b
Grants
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Targeted Alpha Therapies and immunological responses: Next-generation cancer treatments
(2024–2027) Advance Queensland Industry Research Fellowships
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Understanding production and application of alpha emitting radionuclides
(2024–2027) ARC Linkage Projects
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(2018–2019) Cure Cancer Australia Foundation
Supervision
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Modulating the Mononuclear Phagocyte System for Improved Nanomaterial Delivery
Doctor Philosophy
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Design of a complex in vitro microfluidic device for the evaluation of polymeric nanoparticles
Doctor Philosophy
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Development of a versatile targeted alpha therapy platform
Doctor Philosophy
Available Projects
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Radiobiology - Understanding the body's response to radiopharmaceuticals
Targeted radionuclide therapies are undergoing rapid growth as next-generation radiotherapeutics for multiple cancers. Targeted alpha-therapeutics (TATs) in particular are highly potent and outperform current clinical options, representing an opportunity to produce a step change in patient outcomes. Despite international research focus on developing TATs, there remains significant knowledge gaps in understanding associated biological and immunological responses which have key impacts on subsequent efficacy. I have multiple ongoing projects working to addresses this by investigating the interplay between TAT and associated localized cellular, inflammation and immune responses. These projects all fall within my research theme of radiobiology and range from assays in molecular and cellular biology, through to preclinical efficacy and molecular imaging studies to probe all aspects of this research question.
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Targeted nanomedicine radiopharmaceuticals – Next generation treatments for cancer
Molecular radiotherapy (MRT) involves targeted delivery of ionising radiation to trigger localised cell death. Targeted irradiation is achieved using alpha (α) or beta (β-) emitting radionuclides that are incorporated into a radiopharmaceutical. While most MRT research to date has focused on the delivery of β--emitting radionuclides (e.g. 177Lu), growing interest has been focused on α-emitting radionuclides such as 225Ac and 212Pb. Highly ionizing α-particles deposit 100–1000 times greater energy per unit path length than the current clinical standard β- particles, which gives them the ability to produce lethal DNA double-strand breaks within the cell nucleus while reducing the amount of unwanted radiation to surrounding tissues.
Such MRT approaches require a targeting platform to delivery radiotherapeutic payloads. Recently we have demonstrated 212Pb-loaded nanomedicines with excellent efficacy in preclinical models, showing complete tumour regression in many cases. Projects in this space will work on expanding this MRT platform through optimization of materials and dosing regimens as well and producing novel targeting ligands to target a wider range of cancer types. These projects fall within my research theme of nanomedicines and radiopharmaceutical development, involving work ranging from bioengineering and polymer synthesis through to preclinical efficacy and molecular imaging studies to develop potent next-generation nanomedicine radiopharmaceuticals.
Publications
Book Chapter
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Molecular imaging utilizing aptamer-targeted probes
Fletcher, Nicholas and Thurechta, Kristofer (2016). Molecular imaging utilizing aptamer-targeted probes. Aptamers: tools for nanotherapy and molecular imaging. (pp. 287-317) edited by Rakesh N. Veedu. Singapore: Pan Stanford Publishing. doi: 10.1201/b20047-11
Journal Article
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Forgham, Helen, Zhu, Jiayuan, Huang, Xumin, Zhang, Cheng, Biggs, Heather, Liu, Liwei, Wang, Yi Cheng, Fletcher, Nicholas, Humphries, James, Cowin, Gary, Mardon, Karine, Kavallaris, Maria, Thurecht, Kristofer, Davis, Thomas P. and Qiao, Ruirui (2024). Multifunctional Fluoropolymer‐Engineered Magnetic Nanoparticles to Facilitate Blood‐Brain Barrier Penetration and Effective Gene Silencing in Medulloblastoma. Advanced Science, e2401340. doi: 10.1002/advs.202401340
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Wood, James Liam, Ghosh, Saikat, Houston, Zachary, Fletcher, Nicholas, Humphries, James, Mardon, Karine, Akhter, Dewan T., Tieu, William, Ivashkevich, Alesia, Wheatcroft, Michael P., Thurecht, Kristofer J. and Codd, Rachel (2024). A first-in-class dual-chelator theranostic agent designed for use with imaging-therapy radiometal pairs of different elements. Chemical Science. doi: 10.1039/d4sc02851a
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Mint, Kelly, Morrow, Joshua P., Warne, Nicole M., He, Xie, Pizzi, David, Shah, Shaffiq Zainal Osman, Pierens, Gregory K., Fletcher, Nicholas L., Bell, Craig A., Thurecht, Kristofer J. and Kempe, Kristian (2024). Comparison of the hydrophilicity of water-soluble poly(2-alkyl-2-oxazoline)s, poly(2-alkyl-2-oxazine)s and poly(2,4-dialkyl-2-oxazoline)s. Polymer Chemistry. doi: 10.1039/d4py00332b
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Self-cyclisation as a general and efficient platform for peptide and protein macrocyclisation
Jia, Xinying, Chin, Yanni K.-Y., Zhang, Alan H., Crawford, Theo, Zhu, Yifei, Fletcher, Nicholas L., Zhou, Zihan, Hamilton, Brett R., Stroet, Martin, Thurecht, Kristofer J. and Mobli, Mehdi (2023). Self-cyclisation as a general and efficient platform for peptide and protein macrocyclisation. Communications Chemistry, 6 (1) 48, 1-10. doi: 10.1038/s42004-023-00841-5
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Targeted hyperbranched nanoparticles for delivery of doxorubicin in breast cancer brain metastasis
Lim, Malcolm, Fletcher, Nicholas L., Saunus, Jodi M., McCart Reed, Amy E., Chittoory, Haarika, Simpson, Peter T., Thurecht, Kristofer J. and Lakhani, Sunil R. (2023). Targeted hyperbranched nanoparticles for delivery of doxorubicin in breast cancer brain metastasis. Molecular Pharmaceutics, 20 (12), 6169-6183. doi: 10.1021/acs.molpharmaceut.3c00558
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An immunomodulating peptide with potential to suppress tumour growth and autoimmunity
Agrez, Michael, Chandler, Christopher, Thurecht, Kristofer J., Fletcher, Nicholas L., Liu, Feifei, Subramaniam, Gayathri, Howard, Christopher B., Blyth, Benjamin, Parker, Stephen, Turner, Darryl, Rzepecka, Justyna, Knox, Gavin, Nika, Anastasia, Hall, Andrew M., Gooding, Hayley and Gallagher, Laura (2023). An immunomodulating peptide with potential to suppress tumour growth and autoimmunity. Scientific Reports, 13 (1) 19741, 19741. doi: 10.1038/s41598-023-47229-y
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Balaji, Arunpandian, Bell, Craig A., Houston, Zachary H., Bridle, Kim R., Genz, Berit, Fletcher, Nicholas L., Ramm, Grant A. and Thurecht, Kristofer J. (2023). Exploring the impact of severity in hepatic fibrosis disease on the intrahepatic distribution of novel biodegradable nanoparticles targeted towards different disease biomarkers. Biomaterials, 302 122318, 1-18. doi: 10.1016/j.biomaterials.2023.122318
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Huda, Pie, Humphries, James, Fletcher, Nicholas L., Howard, Christopher B., Thurecht, Kristofer J. and Bell, Craig A. (2023). Click‐on antibody fragments for customisable targeted nanomedicines – site‐specific tetrazine and azide functionalisation through non‐canonical amino acid incorporation. Chemistry–Methods, 4 (2) e202300036. doi: 10.1002/cmtd.202300036
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An immunomodulating peptide to counteract solar radiation-induced immunosuppression and DNA damage
Agrez, Michael, Rybchyn, Mark Stephen, De Silva, Warusavithana Gunawardena Manori, Mason, Rebecca Sara, Chandler, Christopher, Piva, Terrence J., Thurecht, Kristofer, Fletcher, Nicholas, Liu, Feifei, Subramaniam, Gayathri, Howard, Christopher B., Blyth, Benjamin, Parker, Stephen, Turner, Darryl, Rzepecka, Justyna, Knox, Gavin, Nika, Anastasia, Hall, Andrew, Gooding, Hayley and Gallagher, Laura (2023). An immunomodulating peptide to counteract solar radiation-induced immunosuppression and DNA damage. Scientific Reports, 13 (1) 11702, 1-19. doi: 10.1038/s41598-023-38890-4
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Ardana, Aditya, Ghosh, Saikat, Huda, Pie, Fletcher, Nicholas L., Thurecht, Kristofer J. and Williams, Charlotte C. (2023). RAFT polymer–antibody conjugation: squaramide ester chemistry leads to conjugates with a therapeutic anti-EGFR antibody with full retention of activity and increased tumor uptake in vivo. Molecular Pharmaceutics, 20 (6), 3073-3087. doi: 10.1021/acs.molpharmaceut.3c00085
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Chu, Weijing, Houston, Zachary H., Fletcher, Nicholas L., Huda, Pie, Ahamed, Muneer, Lim, Ting Xiang, Day, Bryan W., Pinkham, Mark and Thurecht, Kristofer J. (2023). Development and validation of a targeted treatment for brain tumors using a multi-drug loaded, relapse-resistant polymeric theranostic. Biomacromolecules, 24 (6), 2674-2690. doi: 10.1021/acs.biomac.3c00138
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Efficient delivery of Temozolomide using ultrasmall large-pore silica nanoparticles for glioblastoma
Janjua, Taskeen Iqbal, Cao, Yuxue, Ahmed-Cox, Aria, Raza, Aun, Moniruzzaman, Md, Akhter, Dewan Taslima, Fletcher, Nicholas L., Kavallaris, Maria, Thurecht, Kristofer J. and Popat, Amirali (2023). Efficient delivery of Temozolomide using ultrasmall large-pore silica nanoparticles for glioblastoma. Journal of Controlled Release, 357, 161-174. doi: 10.1016/j.jconrel.2023.03.040
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Ghosh, Saikat, Fletcher, Nicholas L., Huda, Pie, Houston, Zachary H., Howard, Christopher B., Lund, Maria E., Lu, Yanling, Campbell, Douglas H., Walsh, Bradley J. and Thurecht, Kristofer J. (2023). Pharmacokinetics and Biodistribution of Zr-Miltuximab and Its Antibody Fragments as Glypican-1 Targeting Immuno-PET Agents in Glioblastoma. Molecular pharmaceutics, 20 (3), 1549-1563. doi: 10.1021/acs.molpharmaceut.2c00760
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Pizzi, David, Humphries, James, Morrow, Joshua P., Mahmoud, Ayaat M., Fletcher, Nicholas L., Sonderegger, Stefan E., Bell, Craig A., Thurecht, Kristofer J. and Kempe, Kristian (2022). Probing the biocompatibility and immune cell association of chiral, water-soluble, bottlebrush poly(2-oxazoline)s. Biomacromolecules, 24 (1), 246-257. doi: 10.1021/acs.biomac.2c01105
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Mills, Jessica A., Humphries, James, Simpson, Joshua D., Sonderegger, Stefan E., Thurecht, Kristofer J. and Fletcher, Nicholas L. (2022). Modulating macrophage clearance of nanoparticles: comparison of small-molecule and biologic drugs as pharmacokinetic modifiers of soft nanomaterials. Molecular Pharmaceutics, 19 (11), 4080-4097. doi: 10.1021/acs.molpharmaceut.2c00528
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Modeling brain metastasis by internal carotid artery injection of cancer cells
Lim, Malcolm, Fletcher, Nicholas, Reed, Amy Mccart, Flint, Melanie, Thurecht, Kristofer, Saunus, Jodi and Lakhani, Sunil R. (2022). Modeling brain metastasis by internal carotid artery injection of cancer cells. Journal of Visualized Experiments, 2022 (186) e64216. doi: 10.3791/64216
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A novel lipidic peptide with potential to promote balanced effector-regulatory T cell responses
Agrez, Michael, Rzepecka, Justyna, Turner, Darryl, Knox, Gavin, Chandler, Christopher, Howard, Christopher B., Fletcher, Nicholas, Thurecht, Kristofer, Parker, Stephen, Gooding, Hayley and Gallagher, Laura (2022). A novel lipidic peptide with potential to promote balanced effector-regulatory T cell responses. Scientific Reports, 12 (1) 11185, 11185. doi: 10.1038/s41598-022-15455-5
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Pre-targeting of polymeric nanomaterials to balance tumour accumulation and clearance
Fletcher, N. L., Prior, A., Choy, O., Humphries, J., Huda, P., Ghosh, S., Houston, Z. H., Bell, C. A. and Thurecht, K. J. (2022). Pre-targeting of polymeric nanomaterials to balance tumour accumulation and clearance. Chemical Communications, 58 (57), 7912-7915. doi: 10.1039/d2cc02443h
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Ahmed, Salma E., Fletcher, Nicholas L., Prior, Amber R., Huda, Pie, Bell, Craig A. and Thurecht, Kristofer J. (2022). Development of targeted micelles and polymersomes prepared from degradable RAFT-based diblock copolymers and their potential role as nanocarriers for chemotherapeutics. Polymer Chemistry, 13 (27), 4004-4017. doi: 10.1039/d2py00257d
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Investigation of a dual siRNA/chemotherapy delivery system for breast cancer therapy
Zhao, Yongmei, Liu, Tianqing, Ardana, Aditya, Fletcher, Nicholas L., Houston, Zachary H., Blakey, Idriss and Thurecht, Kristofer J. (2022). Investigation of a dual siRNA/chemotherapy delivery system for breast cancer therapy. ACS Omega, 7 (20), 17119-17127. doi: 10.1021/acsomega.2c00620
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Antibody-based formats to target glioblastoma: overcoming barriers to protein drug delivery
Ghosh, Saikat, Huda, Pie, Fletcher, Nicholas L., Howard, Christopher B., Walsh, Bradley, Campbell, Douglas, Pinkham, Mark B. and Thurecht, Kristofer J. (2022). Antibody-based formats to target glioblastoma: overcoming barriers to protein drug delivery. Molecular Pharmaceutics, 19 (5), 1233-1247. doi: 10.1021/acs.molpharmaceut.1c00996
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Hu, Yingjie, Li, Jianhua, Ju, Yi, Houston, Zachary H., Fletcher, Nicholas L., De Rose, Robert, Fernandes, Soraia, Hagemeyer, Christoph E., Alt, Karen, Thurecht, Kristofer J., Cortez-Jugo, Christina and Caruso, Frank (2022). Template-assisted antibody assembly: a versatile approach for engineering functional antibody nanoparticles. Chemistry of Materials, 34 (8) acs.chemmater.1c04397, 3694-3704. doi: 10.1021/acs.chemmater.1c04397
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Janowicz, Phillip W., Houston, Zachary H., Bunt, Jens, Fletcher, Nicholas L., Bell, Craig A., Cowin, Gary, Howard, Christopher B., Taslima, Dewan, Westra van Holthe, Nicholas, Prior, Amber, Soh, Vanessa, Ghosh, Saikat, Humphries, James, Huda, Pie, Mahler, Stephen M., Richards, Linda J. and Thurecht, Kristofer J. (2022). Understanding nanomedicine treatment in an aggressive spontaneous brain cancer model at the stage of early blood brain barrier disruption. Biomaterials, 283 121416, 121416. doi: 10.1016/j.biomaterials.2022.121416
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Clinical development of an anti-GPC-1 antibody for the treatment of cancer
Ghosh, Saikat, Huda, Pie, Fletcher, Nicholas, Campbell, Douglas, Thurecht, Kristofer J. and Walsh, Bradley (2022). Clinical development of an anti-GPC-1 antibody for the treatment of cancer. Expert Opinion on Biological Therapy, 22 (5), 603-613. doi: 10.1080/14712598.2022.2033204
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Mills, Jessica A., Liu, Feifei, Jarrett, Thomas R., Fletcher, Nicholas L. and Thurecht, Kristofer J. (2022). Nanoparticle based medicines: approaches for evading and manipulating the mononuclear phagocyte system and potential for clinical translation. Biomaterials Science, 10 (12), 3029-3053. doi: 10.1039/d2bm00181k
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Anane-Adjei, Akosua B., Fletcher, Nicholas L., Cavanagh, Robert J., Houston, Zachary H., Crawford, Theodore, Pearce, Amanda K., Taresco, Vincenzo, Ritchie, Alison A., Clarke, Phillip, Grabowska, Anna M., Gellert, Paul R., Ashford, Marianne B., Kellam, Barrie, Thurecht, Kristofer J. and Alexander, Cameron (2022). Synthesis, characterisation and evaluation of hyperbranched N-(2-hydroxypropyl) methacrylamides for transport and delivery in pancreatic cell lines in vitro and in vivo. Biomaterials Science, 10 (9), 2328-2344. doi: 10.1039/d1bm01548f
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Simpson, Joshua D., Currin-Ross, Denni L., Ediriweera, Gayathri R., Schirra, Horst Joachim, Fletcher, Nicholas L., Bell, Craig A., Arno, Maria C. and Thurecht, Kristofer J. (2021). Cyanine-5-driven behaviours of hyperbranched polymers designed for therapeutic delivery are cell-type specific and correlated with polar lipid distribution in membranes. Nanomaterials, 11 (7) 1745, 1-18. doi: 10.3390/nano11071745
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Evaluation of the in vivo fate of ultrapure alginate in a BALB/c mouse model
A, Anitha, Fletcher, Nicholas L., Houston, Zachary H., Thurecht, Kristofer J. and Grøndahl, Lisbeth (2021). Evaluation of the in vivo fate of ultrapure alginate in a BALB/c mouse model. Carbohydrate Polymers, 262 117947, 117947. doi: 10.1016/j.carbpol.2021.117947
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Pizzi, David, Mahmoud, Ayaat M., Klein, Tobias, Morrow, Joshua P., Humphries, James, Houston, Zachary H., Fletcher, Nicholas L., Bell, Craig A., Thurecht, Kristofer J. and Kempe, Kristian (2021). Poly(2-ethyl-2-oxazoline) bottlebrushes: How nanomaterial dimensions can influence biological interactions. European Polymer Journal, 151 110447, 1-9. doi: 10.1016/j.eurpolymj.2021.110447
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Simpson, Joshua D., Monteiro, Patrícia F., Ediriweera, Gayathri R., Prior, Amber R., Sonderegger, Stefan E., Bell, Craig A., Fletcher, Nicholas L., Alexander, Cameron and Thurecht, Kristofer J. (2021). Fluorophore selection and incorporation contribute to permeation and distribution behaviors of hyperbranched polymers in multi-cellular tumor spheroids and xenograft tumor models. ACS Applied Bio Materials, 4 (3) acsabm.0c01616, 2675-2685. doi: 10.1021/acsabm.0c01616
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Mody, Karishma T., Zhang, Bing, Li, Xun, Fletcher, Nicholas L., Akhter, Dewan T., Jarrett, Sandy, Zhang, Jun, Yu, Chengzhong, Thurecht, Kristofer J., Mahony, Timothy J and Mitter, Neena (2021). Characterization of the biodistribution of a silica vesicle Nanovaccine carrying a Rhipicephalus (Boophilus) microplus protective antigen with in vivo live animal imaging. Frontiers in Bioengineering and Biotechnology, 8 606652, 1-11. doi: 10.3389/fbioe.2020.606652
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dos Santos, Aline Martins, Meneguin, Andréia Bagliotti, Akhter, Dewan Taslima, Fletcher, Nicholas, Houston, Zachary H., Bell, Craig, Thurecht, Kristofer J. and Gremião, Maria Palmira Daflon (2021). Understanding the role of colon-specific microparticles based on retrograded starch/pectin in the delivery of chitosan nanoparticles along the gastrointestinal tract. European Journal of Pharmaceutics and Biopharmaceutics, 158, 371-378. doi: 10.1016/j.ejpb.2020.12.004
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Deepagan, Veerasikku Gopal, Leiske, Meike N., Fletcher, Nicholas L., Rudd, David, Tieu, Terence, Kirkwood, Nicholas, Thurecht, Kristofer J., Kempe, Kristian, Voelcker, Nicolas H. and Cifuentes-Rius, Anna (2020). Engineering fluorescent gold nanoclusters using xanthate-functionalized hydrophilic polymers: toward enhanced monodispersity and stability. Nano Letters, 21 (1) acs.nanolett.0c03930, 476-484. doi: 10.1021/acs.nanolett.0c03930
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Marasini, Nirmal, Fu, Changkui, Fletcher, Nicholas L., Subasic, Christopher, Er, Gerald, Mardon, Karine, Thurecht, Kristofer J., Whittaker, Andrew K. and Kaminskas, Lisa M. (2020). The impact of polymer size and cleavability on the intravenous pharmacokinetics of PEG-based hyperbranched polymers in rats. Nanomaterials, 10 (12) 2452, 1-16. doi: 10.3390/nano10122452
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Sivaram, Amal J., Wardiana, Andri, Preethi, S. S. Hema, Fuchs, Adrian V., Howard, Christopher B., Fletcher, Nicholas L., Bell, Craig A. and Thurecht, Kristofer J. (2020). Effect of chain‐end chemistries on the efficiency of coupling antibodies to polymers using unnatural amino acids. Macromolecular Rapid Communications, 41 (21) 2000294, e2000294. doi: 10.1002/marc.202000294
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Controlling the biological fate of micellar nanoparticles: balancing stealth and targeting
Sivaram, Amal J., Wardiana, Andri, Alcantara, Sheilajen, Sonderegger, Stefan E., Fletcher, Nicholas L., Houston, Zachary H., Howard, Christopher B., Mahler, Stephen M., Alexander, Cameron, Kent, Stephen J., Bell, Craig A. and Thurecht, Kristofer J. (2020). Controlling the biological fate of micellar nanoparticles: balancing stealth and targeting. ACS Nano, 14 (10) acsnano.0c06033, 13739-13753. doi: 10.1021/acsnano.0c06033
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Next‐generation polymeric nanomedicines for oncology: perspectives and future directions
Fletcher, Nicholas L., Kempe, Kristian and Thurecht, Kristofer J. (2020). Next‐generation polymeric nanomedicines for oncology: perspectives and future directions. Macromolecular Rapid Communications, 41 (18) 2000319, 2000319. doi: 10.1002/marc.202000319
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Humphries, James, Pizzi, David, Sonderegger, Stefan E., Fletcher, Nicholas L., Houston, Zachary H., Bell, Craig A., Kempe, Kristian and Thurecht, Kristofer J. (2020). Hyperbranched Poly(2-oxazoline)s and Poly(ethylene glycol): A structure–activity comparison of biodistribution. Biomacromolecules, 21 (8) acs.biomac.0c00765, 3318-3331. doi: 10.1021/acs.biomac.0c00765
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Noy, Janina-Miriam, Chen, Fan, Akhter, Dewan T., Houston, Zachary H., Fletcher, Nicholas L., Thurecht, Kristofer J. and Stenzel, Martina H. (2020). Direct comparison of poly(ethylene glycol) and phosphorylcholine drug-loaded nanoparticles in vitro and in vivo. Biomacromolecules, 21 (6) acs.biomac.0c00257, 2320-2333. doi: 10.1021/acs.biomac.0c00257
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Leiske, Meike N., Walker, Julia A., Zia, Aadarash, Fletcher, Nicholas L., Thurecht, Kristofer J., Davis, Thomas P. and Kempe, Kristian (2020). Synthesis of biscarboxylic acid functionalised EDTA mimicking polymers and their ability to form Zr(iv) chelation mediated nanostructures. Polymer Chemistry, 11 (16), 2799-2810. doi: 10.1039/d0py00304b
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Houston, Zachary H., Bunt, Jens, Chen, Kok-Siong, Puttick, Simon, Howard, Christopher B., Fletcher, Nicholas L., Fuchs, Adrian V., Cui, Jiwei, Ju, Yi, Cowin, Gary, Song, Xin, Boyd, Andrew W., Mahler, Stephen M., Richards, Linda J., Caruso, Frank and Thurecht, Kristofer J. (2020). Understanding the uptake of nanomedicines at different stages of brain cancer using a modular nanocarrier platform and precision bispecific antibodies. ACS Central Science, 6 (5) acscentsci.9b01299, 727-738. doi: 10.1021/acscentsci.9b01299
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Zhao, Yongmei, Fletcher, Nicholas L., Gemmell, Anna, Houston, Zachary H., Howard, Christopher B., Blakey, Idriss, Liu, Tianqing and Thurecht, Kristofer J. (2020). Investigation of the therapeutic potential of a synergistic delivery system through dual controlled release of camptothecin-doxorubicin. Advanced Therapeutics, 3 (6) 1900202, 1900202. doi: 10.1002/adtp.201900202
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Akhter, Dewan T., Simpson, Joshua D., Fletcher, Nicholas L., Houston, Zachary H., Fuchs, Adrian V., Bell, Craig A. and Thurecht, Kristofer J. (2020). Oral delivery of multicompartment nanomedicines for colorectal cancer therapeutics: combining loco-regional delivery with cell-target specificity. Advanced Therapeutics, 3 (2) ARTN 1900171, 1900171. doi: 10.1002/adtp.201900171
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Ediriweera, Gayathri R., Simpson, Joshua D., Fuchs, Adrian V., Venkatachalam, Taracad K., Van De Walle, Matthias, Howard, Christopher B., Mahler, Stephen M., Blinco, James P., Fletcher, Nicholas L., Houston, Zachary H., Bell, Craig A. and Thurecht, Kristofer J. (2020). Targeted and modular architectural polymers employing bioorthogonal chemistry for quantitative therapeutic delivery. Chemical Science, 11 (12), 3268-3280. doi: 10.1039/d0sc00078g
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Yeh, Mei-Chun, Tse, Brian W. C., Fletcher, Nicholas L., Houston, Zachary H., Lund, Maria, Volpert, Marianna, Stewart, Chelsea, Sokolowski, Kamil A., Jeet, Varinder, Thurecht, Kristofer J., Campbell, Douglas H., Walsh, Bradley J., Nelson, Colleen C. and Russell, Pamela J. (2020). Targeted beta therapy of prostate cancer with 177Lu-labelled Miltuximab® antibody against glypican-1 (GPC-1). EJNMMI Research, 10 (1) 46, 46. doi: 10.1186/s13550-020-00637-x
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Pizzi, David, Humphries, James, Morrow, Joshua P., Fletcher, Nicholas L., Bell, Craig A., Thurecht, Kristofer J. and Kempe, Kristian (2019). Poly(2-oxazoline) macromonomers as building blocks for functional and biocompatible polymer architectures. European Polymer Journal, 121 109258, 109258. doi: 10.1016/j.eurpolymj.2019.109258
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Simpson, Joshua D., Ediriweera, Gayathri R., Howard, Christopher B., Fletcher, Nicholas L., Bell, Craig A. and Thurecht, Kristofer J. (2019). Polymer design and component selection contribute to uptake, distribution & trafficking behaviours of polyethylene glycol hyperbranched polymers in live MDA-MB-468 breast cancer cells. Biomaterials Science, 7 (11), 4661-4674. doi: 10.1039/c9bm00957d
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Modulating targeting of poly(ethylene glycol) particles to tumor cells using bispecific antibodies
Cui, Jiwei, Ju, Yi, Houston, Zachary H., Glass, Joshua J., Fletcher, Nicholas L., Alcantara, Sheilajen, Dai, Qiong, Howard, Christopher B., Mahler, Stephen M., Wheatley, Adam K., De Rose, Robert, Brannon, Paul T., Paterson, Brett M., Donnelly, Paul S., Thurecht, Kristofer J., Caruso, Frank and Kent, Stephen J. (2019). Modulating targeting of poly(ethylene glycol) particles to tumor cells using bispecific antibodies. Advanced Healthcare Materials, 8 (9) 1801607, e1801607. doi: 10.1002/adhm.201801607
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Ultrasound-responsive nanobubbles for enhanced intravitreal drug migration: An ex vivo evaluation
Thakur, Sachin S., Chen, Ying-Shan, Houston, Zachary H., Fletcher, Nicholas, Barnett, Nigel L., Thurecht, Kristofer J., Rupenthal, Ilva D. and Parekh, Harendra S. (2019). Ultrasound-responsive nanobubbles for enhanced intravitreal drug migration: An ex vivo evaluation. European Journal of Pharmaceutics and Biopharmaceutics, 136, 102-107. doi: 10.1016/j.ejpb.2019.01.014
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Crawford, Theo, Fletcher, Nicholas, Veitch, Margaret, Gonzalez Cruz, Jazmina L., Pett, Nicola, Brereton, Ian, Wells, James W., Mobli, Mehdi and Tesiram, Yasvir (2019). Bacillus anthracis Protective Antigen Shows High Specificity for a UV Induced Mouse Model of Cutaneous Squamous Cell Carcinoma. Frontiers in Medicine, 6 (FEB) 22, 22. doi: 10.3389/fmed.2019.00022
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Lu, Mingxia, Chen, Fan, Cao, Cheng, Garvey, Christopher J., Fletcher, Nicholas L., Houston, Zachary H., Lu, Hongxu, Lord, Megan S., Thurecht, Kristofer J. and Stenzel, Martina H. (2019). Importance of polymer length in fructose-based polymeric micelles for an enhanced biological activity. Macromolecules, 52 (2) acs.macromol.8b02381, 477-486. doi: 10.1021/acs.macromol.8b02381
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RNA interference to enhance radiation therapy: targeting the DNA damage response
Ratnayake, G., Bain, A. L., Fletcher, N., Howard, C. B., Khanna, K. K. and Thurecht, K. J. (2018). RNA interference to enhance radiation therapy: targeting the DNA damage response. Cancer Letters, 439, 14-23. doi: 10.1016/j.canlet.2018.09.011
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Influence of Charge on Hemocompatibility and Immunoreactivity of Polymeric Nanoparticles
Chen, Liyu, Glass, Joshua J., De Rose, Robert, Sperling, Claudia, Kent, Stephen J., Houston, Zachary H., Fletcher, Nicholas L., Rolfe, Barbara E. and Thurecht, Kristofer J. (2018). Influence of Charge on Hemocompatibility and Immunoreactivity of Polymeric Nanoparticles. ACS Applied Bio Materials, 1 (3) acsabm.8b00220, 756-767. doi: 10.1021/acsabm.8b00220
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Zhao, Yongmei, Fletcher, Nicholas L., Liu, Tianqing, Gemmell, Anna C., Houston, Zachary H., Blakey, Idriss and Thurecht, Kristofer J. (2018). In vivo therapeutic evaluation of polymeric nanomedicines: effect of different targeting peptides on therapeutic efficacy against breast cancer. Nanotheranostics, 2 (4), 360-370. doi: 10.7150/ntno.27142
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Blackman, Lewis D., Varlas, Spyridon, Arno, Maria C., Houston, Zachary H., Fletcher, Nicholas L., Thurecht, Kristofer J., Hasan, Muhammad, Gibson, Matthew I. and O’Reilly, Rachel K. (2018). Confinement of therapeutic enzymes in selectively permeable polymer vesicles by Polymerization-Induced Self-Assembly (PISA) reduces antibody binding and proteolytic susceptibility. ACS Central Science, 4 (6), 718-723. doi: 10.1021/acscentsci.8b00168
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Modified organosilica core-shell nanoparticles for stable pH sensing in biological solutions
Robinson, Kye J., Huynh, Gabriel T., Kouskousis, Betty P., Fletcher, Nicholas L., Houston, Zachary H., Thurecht, Kristofer J. and Corrie, Simon R. (2018). Modified organosilica core-shell nanoparticles for stable pH sensing in biological solutions. ACS Sensors, 3 (5), 967-975. doi: 10.1021/acssensors.8b00034
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Fletcher, N. L., Houston, Z. H., Simpson, J. D., Veedu, R. N. and Thurecht, K. J. (2018). Designed multifunctional polymeric nanomedicines: long-term biodistribution and tumour accumulation of aptamer-targeted nanomaterials. Chemical Communications, 54 (82), 11538-11541. doi: 10.1039/c8cc05831h
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Polynitroxide copolymers to reduce biofilm fouling on surfaces
Boase, Nathan R. B., Torres, Marcelo D. T., Fletcher, Nicholas L., de la Fuente-Nunez, Cesar and Fairfull-Smith, Kathryn E. (2018). Polynitroxide copolymers to reduce biofilm fouling on surfaces. Polymer Chemistry, 9 (43), 5308-5318. doi: 10.1039/c8py01101j
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Gold Nanocluster-Mediated Cellular Death under Electromagnetic Radiation
Cifuentes-Rius, Anna, Ivask, Angela, Das, Shreya, Penya-Auladell, Nuria, Fabregas, Laura, Fletcher, Nicholas L., Houston, Zachary H., Thurecht, Kristofer J. and Voelcker, Nicolas H. (2017). Gold Nanocluster-Mediated Cellular Death under Electromagnetic Radiation. Acs Applied Materials & Interfaces, 9 (47), 41159-41167. doi: 10.1021/acsami.7b13100
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Pearce, Amanda K., Simpson, Joshua D., Fletcher, Nicholas L., Houston, Zachary H., Fuchs, Adrian V., Russell, Pamela J., Whittaker, Andrew K. and Thurecht, Kristofer J. (2017). Localised delivery of doxorubicin to prostate cancer cells through a PSMA-targeted hyperbranched polymer theranostic. Biomaterials, 141, 330-339. doi: 10.1016/j.biomaterials.2017.07.004
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Zhao, Yongmei, Houston, Zachary H., Simpson, Joshua D., Chen, Liyu, Fletcher, Nicholas L., Fuchs, Adrian V., Blakey, Idriss and Thurecht, Kristofer J. (2017). Using peptide aptamer targeted polymers as a model nanomedicine for investigating drug distribution in cancer nanotheranostics. Molecular Pharmaceutics, 14 (10), 3539-3549. doi: 10.1021/acs.molpharmaceut.7b00560
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Dexter, A. F., Fletcher, N. L., Creasey, R. G., Filardo, F., Boehm, M. W. and Jack, K. S. (2017). Fabrication and characterization of hydrogels formed from designer coiled-coil fibril-forming peptides. RSC Advances, 7 (44), 27260-27271. doi: 10.1039/c7ra02811c
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Preclinical imaging of siRNA delivery
Fletcher, Nicholas, Ardana, Aditya and Thurecht, Kristofer J. (2016). Preclinical imaging of siRNA delivery. Australian Journal of Chemistry, 69 (10), 1073-1077. doi: 10.1071/CH16079
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Howard, Christopher B., Fletcher, Nicholas, Houston, Zachary H., Fuchs, Adrian V., Boase, Nathan R. B., Simpson, Joshua D., Raftery, Lyndon J., Ruder, Tim, Jones, Martina L., de Bakker, Christopher J., Mahler, Stephen M. and Thurecht, Kristofer J. (2016). Targeted nanomaterials: overcoming instability of antibody-nanomaterial conjugates: next generation targeted nanomedicines using bispecific antibodies (Adv. Healthcare Mater. 16/2016). Advanced Healthcare Materials, 5 (16), 1994-1994. doi: 10.1002/adhm.201670084
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Howard, Christopher B., Fletcher, Nicholas, Houston, Zachary H., Fuchs, Adrian V., Boase, Nathan R. B., Simpson, Joshua D., Raftery, Lyndon J., Ruder, Tim, Jones, Martina L., de Bakker, Christopher J., Mahler, Stephen M. and Thurecht, Kristofer J. (2016). Overcoming Instability of Antibody-Nanomaterial Conjugates: Next Generation Targeted Nanomedicines Using Bispecific Antibodies. Advanced Healthcare Materials, 5 (16), 2055-2068. doi: 10.1002/adhm.201600263
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Pearce, Amanda K., Fuchs, Adrian V., Fletcher, Nicholas L. and Thurecht, Kristofer J. (2016). Targeting Nanomedicines to Prostate Cancer: Evaluation of Specificity of Ligands to Two Different Receptors In Vivo. Pharmaceutical Research, 33 (10), 1-12. doi: 10.1007/s11095-016-1945-x
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Synthesis, characterization and biological activities of semicarbazones and their copper complexes
Venkatachalam, Taracad K., Bernhardt, Paul V., Noble, Chris J., Fletcher, Nicholas, Pierens, Gregory K., Thurecht, Kris J. and Reutens, David C. (2016). Synthesis, characterization and biological activities of semicarbazones and their copper complexes. Journal of Inorganic Biochemistry, 162, 295-308. doi: 10.1016/j.jinorgbio.2016.04.006
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Evaluation of polymeric nanomedicines targeted to PSMA: effect of ligand on targeting efficiency
Fuchs, Adrian V., Tse, Brian W.C., Pearce, Amanda. K., Yeh, Mei-Chun, Fletcher, Nicholas L., Huang, Steve S., Heston, Warren D., Whittaker, Andrew K., Russell, Pamela J. and Thurecht, Kristofer J. (2015). Evaluation of polymeric nanomedicines targeted to PSMA: effect of ligand on targeting efficiency. Biomacromolecules, 16 (10), 3235-3247. doi: 10.1021/acs.biomac.5b00913
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Fletcher, Nicholas L., Paquet, Nicolas, Dickinson, Ellyce L. and Dexter, Annette F. (2015). Bioproduction of highly charged designer peptide surfactants via a chemically cleavable coiled-coil heteroconcatemer. Biotechnology and Bioengineering, 112 (2), 242-251. doi: 10.1002/bit.25446
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A pH-responsive coiled-coil peptide hydrogel
Fletcher, Nicholas L., Lockett, Christina V. and Dexter, Annette F. (2011). A pH-responsive coiled-coil peptide hydrogel. Soft Matter, 7 (21), 10210-10218. doi: 10.1039/c1sm06261a
Conference Publication
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Canine PET/CT imaging with 64Cu-nanomedicines
Daniel, Sarah, Houston, Zachary, Fletcher, Nicholas, Bell, Craig, Atcheson, Nicole, Al-Najjar, Aiman, Howard, Christopher, Mahler, Stephen, Straw, Rod and Thurecht, Kristofer (2020). Canine PET/CT imaging with 64Cu-nanomedicines. SNMMI Annual Meeting, Online, 11-14 July, 2020. Reston, VA, United States: Society of Nuclear Medicine.
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Yeh, Mei-Chun, Tse, Brian W. C., Fletcher, Nicholas L., Huston, Zachary H., Stewart, Chelsea, Sokolowski, Kamil, Jeet, Varinder, Wissmueller, Sandra, Thurecht, Kristofer J., Campbell, Douglas H., Walsh, Bradley J., Nelson, Colleen C. and Russell, Pamela J. (2018). Targeted beta therapy of human prostate cancer in vivo with Lu-177 labelled MIL-38 antibody against glypican-1 (GPC-1). 19th Asia-Pacific Prostate Cancer Conference, Brisbane Australia, Aug 22-25, 2018. HOBOKEN: WILEY.
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Design-led 3D visualization of nanomedicines in virtual reality
Lilja, Andrew R., Strong, Campbell W., Bailey, Benjamin J., Thurecht, Kristofer J., Houston, Zachary H., Fletcher, Nicholas L. and McGhee, John B. (2018). Design-led 3D visualization of nanomedicines in virtual reality. 24th ACM Symposium on Virtual Reality Software and Technology (ACM VRST), Tokyo, Japan, Nov 28- Dec 01 2018. New York, NY, United States: Association for Computing Machinery. doi: 10.1145/3281505.3281572
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Development of polymer theranostics to probe the behaviour of nanomaterials in biology
Thurecht, Kristofer, Zhou, Yongmei, Fletcher, Nicholas and Houston, Zachary (2018). Development of polymer theranostics to probe the behaviour of nanomaterials in biology. 255th National Meeting and Exposition of the American-Chemical-Society (ACS) - Nexus of Food, Energy, and Water, New Orleans, LA United States, 18-22 March 2018. Washington, DC United States: American Chemical Society.
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Evaluation of the in vivo fate of ultrapure alginate in mice model
Anitha, A., Fletcher, Nicholas, Houston, Zachary, Thurecht, Kristofer and Grondahl, Lisbeth (2016). Evaluation of the in vivo fate of ultrapure alginate in mice model. 10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May 2016. Lausanne, Switzerland: Frontiers Research Foundation. doi: 10.3389/conf.FBIOE.2016.01.02237
Other Outputs
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Bioproduction and self-assembly of designer peptides
Fletcher, Nicholas (2015). Bioproduction and self-assembly of designer peptides. PhD Thesis, Australian Institute for Bioengineering and Nanotechnology, The University of Queensland. doi: 10.14264/uql.2015.436
Grants (Administered at UQ)
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Targeted Alpha Therapies and immunological responses: Next-generation cancer treatments
(2024–2027) Advance Queensland Industry Research Fellowships
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Understanding production and application of alpha emitting radionuclides
(2024–2027) ARC Linkage Projects
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(2018–2019) Cure Cancer Australia Foundation
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(2017–2018) UQ Early Career Researcher
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2011 UQ Trans-Pacific Fellowship - Peptide hydrogels as wound healing matrices
(2011–2012) UQ Trans-Pacific Fellowship
PhD and MPhil Supervision
Current Supervision
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Modulating the Mononuclear Phagocyte System for Improved Nanomaterial Delivery
Doctor Philosophy — Principal Advisor
Other advisors:
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Design of a complex in vitro microfluidic device for the evaluation of polymeric nanoparticles
Doctor Philosophy — Associate Advisor
Other advisors:
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Development of a versatile targeted alpha therapy platform
Doctor Philosophy — Associate Advisor
Other advisors:
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Molecular alpha radiotherapy using nanomaterials mediated via pre-targeting strategy
Doctor Philosophy — Associate Advisor
Other advisors:
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The effect of avidity on nanobody-based formats for theranostic applications
Doctor Philosophy — Associate Advisor
Other advisors:
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Novel complementary diagnostics for improved therapeutics/theranostics
Doctor Philosophy — Associate Advisor
Other advisors:
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Targeted polymeric radiopharmaceutical as cancer theranostics
Doctor Philosophy — Associate Advisor
Other advisors:
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Development of site-specific radiopharmaceuticals using nanotechnology
Doctor Philosophy — Associate Advisor
Other advisors:
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Novel low-fouling biopolymers for biomedical applications
Doctor Philosophy — Associate Advisor
Other advisors:
Completed Supervision
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(2023) Doctor Philosophy — Associate Advisor
Other advisors:
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Developing nanomedicines for cancer theranostics
(2023) Doctor Philosophy — Associate Advisor
Other advisors:
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Understanding Immunogenicity in Nanomedicine
(2023) Doctor Philosophy — Associate Advisor
Other advisors:
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Biological Interactions of Polymeric Nanomedicines & Molecular Imaging Agents
(2021) Doctor Philosophy — Associate Advisor
Other advisors:
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Investigating the delivery and mechanisms of novel dementia and glioblastoma therapeutics
(2021) Doctor Philosophy — Associate Advisor
Other advisors:
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Radiosensitization of Prostate Cancer by Nanoparticle Mediated RNA Interference
(2019) Master Philosophy — Associate Advisor
Possible Research Projects
Note for students: The possible research projects listed on this page may not be comprehensive or up to date. Always feel free to contact the staff for more information, and also with your own research ideas.
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Radiobiology - Understanding the body's response to radiopharmaceuticals
Targeted radionuclide therapies are undergoing rapid growth as next-generation radiotherapeutics for multiple cancers. Targeted alpha-therapeutics (TATs) in particular are highly potent and outperform current clinical options, representing an opportunity to produce a step change in patient outcomes. Despite international research focus on developing TATs, there remains significant knowledge gaps in understanding associated biological and immunological responses which have key impacts on subsequent efficacy. I have multiple ongoing projects working to addresses this by investigating the interplay between TAT and associated localized cellular, inflammation and immune responses. These projects all fall within my research theme of radiobiology and range from assays in molecular and cellular biology, through to preclinical efficacy and molecular imaging studies to probe all aspects of this research question.
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Targeted nanomedicine radiopharmaceuticals – Next generation treatments for cancer
Molecular radiotherapy (MRT) involves targeted delivery of ionising radiation to trigger localised cell death. Targeted irradiation is achieved using alpha (α) or beta (β-) emitting radionuclides that are incorporated into a radiopharmaceutical. While most MRT research to date has focused on the delivery of β--emitting radionuclides (e.g. 177Lu), growing interest has been focused on α-emitting radionuclides such as 225Ac and 212Pb. Highly ionizing α-particles deposit 100–1000 times greater energy per unit path length than the current clinical standard β- particles, which gives them the ability to produce lethal DNA double-strand breaks within the cell nucleus while reducing the amount of unwanted radiation to surrounding tissues.
Such MRT approaches require a targeting platform to delivery radiotherapeutic payloads. Recently we have demonstrated 212Pb-loaded nanomedicines with excellent efficacy in preclinical models, showing complete tumour regression in many cases. Projects in this space will work on expanding this MRT platform through optimization of materials and dosing regimens as well and producing novel targeting ligands to target a wider range of cancer types. These projects fall within my research theme of nanomedicines and radiopharmaceutical development, involving work ranging from bioengineering and polymer synthesis through to preclinical efficacy and molecular imaging studies to develop potent next-generation nanomedicine radiopharmaceuticals.
