Overview
Background
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.
Availability
- Dr Nick Fletcher is:
- Available for supervision
Qualifications
- Bachelor, The University of Queensland
- Doctor of Philosophy, The University of Queensland
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.
Works
Search Professor Nick Fletcher’s works on UQ eSpace
2022
Journal Article
Development of targeted micelles and polymersomes prepared from degradable RAFT-based diblock copolymers and their potential role as nanocarriers for chemotherapeutics
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
2022
Journal Article
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
2022
Journal Article
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
2022
Journal Article
Template-assisted antibody assembly: a versatile approach for engineering functional antibody nanoparticles
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
2022
Journal Article
Understanding nanomedicine treatment in an aggressive spontaneous brain cancer model at the stage of early blood brain barrier disruption
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
2022
Journal Article
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
2022
Journal Article
Synthesis, characterisation and evaluation of hyperbranched N-(2-hydroxypropyl) methacrylamides for transport and delivery in pancreatic cell lines in vitro and in vivo
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
2022
Journal Article
Nanoparticle based medicines: approaches for evading and manipulating the mononuclear phagocyte system and potential for clinical translation
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
2021
Journal Article
Cyanine-5-driven behaviours of hyperbranched polymers designed for therapeutic delivery are cell-type specific and correlated with polar lipid distribution in membranes
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
2021
Journal Article
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
2021
Journal Article
Poly(2-ethyl-2-oxazoline) bottlebrushes: How nanomaterial dimensions can influence biological interactions
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
2021
Journal Article
Fluorophore selection and incorporation contribute to permeation and distribution behaviors of hyperbranched polymers in multi-cellular tumor spheroids and xenograft tumor models
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
2021
Journal Article
Characterization of the biodistribution of a silica vesicle Nanovaccine carrying a Rhipicephalus (Boophilus) microplus protective antigen with in vivo live animal imaging
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
2021
Journal Article
Understanding the role of colon-specific microparticles based on retrograded starch/pectin in the delivery of chitosan nanoparticles along the gastrointestinal tract
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
2020
Journal Article
Engineering fluorescent gold nanoclusters using xanthate-functionalized hydrophilic polymers: toward enhanced monodispersity and stability
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
2020
Journal Article
The impact of polymer size and cleavability on the intravenous pharmacokinetics of PEG-based hyperbranched polymers in rats
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
2020
Journal Article
Effect of chain‐end chemistries on the efficiency of coupling antibodies to polymers using unnatural amino acids
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
2020
Journal Article
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
2020
Journal Article
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
2020
Journal Article
Hyperbranched Poly(2-oxazoline)s and Poly(ethylene glycol): A structure–activity comparison of biodistribution
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
Supervision
Availability
- Dr Nick Fletcher is:
- Available for supervision
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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.
Supervision history
Current supervision
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Doctor Philosophy
Modulating the Mononuclear Phagocyte System for Improved Nanomaterial Delivery
Principal Advisor
Other advisors: Professor Kristofer Thurecht, Associate Professor Barbara Rolfe
-
Doctor Philosophy
Novel complementary diagnostics for improved therapeutics/theranostics
Associate Advisor
Other advisors: Dr Craig Bell, Dr Rhia Stone, Professor Kristofer Thurecht
-
Doctor Philosophy
The effect of avidity on nanobody-based formats for theranostic applications
Associate Advisor
Other advisors: Dr Jodi Saunus, Dr Pie Huda, Professor Kristofer Thurecht
-
Doctor Philosophy
Design of a complex in vitro microfluidic device for the evaluation of polymeric nanoparticles
Associate Advisor
Other advisors: Professor Kristofer Thurecht
-
Doctor Philosophy
Targeted polymeric radiopharmaceutical as cancer theranostics
Associate Advisor
Other advisors: Professor Kristofer Thurecht
-
Doctor Philosophy
Molecular alpha radiotherapy using nanomaterials mediated via pre-targeting strategy
Associate Advisor
Other advisors: Professor Kristofer Thurecht
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Doctor Philosophy
Development of site-specific radiopharmaceuticals using nanotechnology
Associate Advisor
Other advisors: Professor Kristofer Thurecht
-
Doctor Philosophy
Development of a versatile targeted alpha therapy platform
Associate Advisor
Other advisors: Professor David Owen, Dr Pie Huda
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Doctor Philosophy
Novel low-fouling biopolymers for biomedical applications
Associate Advisor
Other advisors: Professor Andrew Whittaker
Completed supervision
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2023
Doctor Philosophy
Understanding Immunogenicity in Nanomedicine
Associate Advisor
Other advisors: Dr Craig Bell, Dr Pie Huda, Professor Kristofer Thurecht
-
2023
Doctor Philosophy
Design of pH-sensitive, polymeric nanoparticles, and their application in chemotherapeutic drug delivery
Associate Advisor
Other advisors: Dr Craig Bell, Professor Kristofer Thurecht
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2023
Doctor Philosophy
Developing nanomedicines for cancer theranostics
Associate Advisor
Other advisors: Professor Kristofer Thurecht
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2021
Doctor Philosophy
Biological Interactions of Polymeric Nanomedicines & Molecular Imaging Agents
Associate Advisor
Other advisors: Dr Craig Bell, Professor Kristofer Thurecht
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2021
Doctor Philosophy
Investigating the delivery and mechanisms of novel dementia and glioblastoma therapeutics
Associate Advisor
Other advisors: Professor Kristofer Thurecht
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2019
Master Philosophy
Radiosensitization of Prostate Cancer by Nanoparticle Mediated RNA Interference
Associate Advisor
Other advisors: Honorary Professor Kum Kum Khanna, Dr Christopher Howard, Professor Kristofer Thurecht
Media
Enquiries
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