Neil Thomas
University of Nottingham
1987 BSc(Hons) Chemistry 1st Class, University of Southampton, UK1990 PhD Mechanistic Enzymology, Southampton (Prof. D. Gani), UK1990-92 NATO/SERC Fellow Pennsylvania State University (Prof. S.J. Benkovic), USA1992-1995 Royal Society University Research Fellow and Lecturer, School of Chemistry, University of Bath, UK1995-2003 Royal Society University Research Fellow and Lecturer, School of Chemistry, University of Nottingham, UK2003-2008 Senior Lecturer/Associate Professor, School of Chemistry, University of Nottingham, UK2008-present Professor of Medicinal & Biological Chemistry, School of Chemistry, Centre for Biomolecular Sciences, University of Nottingham, UK
Introduction
Apoferritin is a ubiquitous protein nanocage, 12 nm in diameter with an 8 nm diameter hollow core that is used in nature as a store for up to 4,500 iron (III) ions forming ferritin. Removal of the Iron(III) ions by reduction leaves the protein cage which reversibly disassembles below pH 4.0. The apoferritin nanocage is very robust being stable in aqueous buffer upto 80 oC and pH 4.5-10.0. A number of groups including ours have encapsulated drugs (gefitinib, doxorubicin, cis-platin) or nanocrystals (magnetic iron, PbS quantum dots) in the apoferritin core using either a 'nanoreactor' or pH shift disassembly-reassembly route. This composites have been shown to be actively uptaken by a range of different cell types, typically via transferrin-receptor mediated endocytosis. Progression through the endosome-lysosome system with a gradual decrease in pH results in the disassembly of the apoferritin and release of its cargo. To take advantage of these 'trojan horse'-like properties we have modified the apoferritin with an affibody that targets the Her2 receptor that is overexpressed in >20% of breast cancer cell lines in order to specifically target tumorogenic cells.
Results and Discussion
By mixing together Her2-modified and unmodified apoferritins in different ratios we can significantly attenuate the biological effects these constructs have on Her2 receptor degradation and downstream signalling which then affects both apoptosis and cell proliferation in vitro. The results of these studies together with those in which the affibody-apoferritins are combined with a variety of cargoes will be presented.
References
An Apoferritin-based Drug Delivery System for the Tyrosine Kinase Inhibitor Gefitinib, Kuruppu, Anchala; Zhang, Lei; Collins, Hilary; Turyanska, Lyudmila; Thomas, Neil R.; Bradshaw, Tracey D. Adv. Healthcare Mat. 2015, 4, 2816-282.
Apoferritin-encapsulated PbS quantum dots significantly inhibit growth of colorectal carcinoma cells, Bradshaw, Tracey D.; Junor, Marc; Patane, Amalia; Clarke, Phil; Thomas, Neil R.; Li, Mei; Mann, Stephen; Turyanska, Lyudmila, J. Mat. Chem. B, 2013, 1, 6254-626
The differential effect of apoferritin-PbS nanocomposites on cell cycle progression in normal and cancerous cells, Turyanska, Lyudmila; Bradshaw, Tracey D.; Li, Mei; Bardelang, Philip; Drewe, William; Patane, Amalia; Thomas, Neil R. J. Mat. Chem. 2012, 22, 660-665.
Targeted drug delivery and nanocarriers , Nanomedicine for cancer diagnosis & therapy , Nano-Imaging for diagnosis, therapy and delivery
