University of Bath PHD New Functionalised Carbon Based Nanomaterials for Biomedical Imaging Applications Ge, Haobo Award date: 2015 Awarding institution: University of Bath Link to publication Alternative formats If you require this document in an alternative format, please contact: [email protected] General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal ? Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Download date: 10. Oct. 2021 New Functionalised Carbon Based Nanomaterials for Biomedical Imaging Applications Haobo Ge A thesis submitted for the degree of Doctor of Philosophy University of Bath Department of Chemistry Jun 2015 Copyright Attention is drawn to the fact that copyright of this thesis rests with the author. A copy of this thesis has been supplied on condition that anyone who consults it is understood to recognise that its copyright rests with the author and that they must not copy it or use material from it except as permitted by law or with the consent of the author. This thesis may be made available for consultation within the University Library and may be photocopied or lent to other libraries for the purposes of consultation with effect from………………. Signed on behalf of the Faculty of Science of................................... University of Bath, Jun 2015 I List of published articles during PhD List of published articles during PhD 1. V. Mirabello, D. G. Calatayud, R. L. Arrowsmith, H. Ge and S. I. Pascu, Metallic nanoparticles as synthetic building blocks for cancer nanodiagnostics: from materials design to molecular imaging applications. Journal of Materials Chemistry B, 2015, DOI: 10.1039/c5tb00841g. 2. Z. Hu, R. L. Arrowsmith, J. A. Tyson, V. Mirabello, H. Ge, I. M. Eggleston, S. W. Botchway, G. D. Pantos and S. I. Pascu, A Fluorescent Arg–Gly–Asp (RGD) Peptide-Naphthalenediimide (NDI) Conjugate for imaging integrin αvβ3 in vitro, Chem. Commun., 2015, 51, 6901-6904. 3. S. Y. Xu, X. Sun, H. Ge, R. L. Arrowsmith, J. S. Fossey, S. I. Pascu, Y. B. Jiang and T. D. James, Synthesis and evaluation of a boronate-tagged 1, 8- naphthalimide probe for fluoride recognition, Organic & biomolecular chemistry, 2015, 13, 4143-4148. 4. K. Lawrence, F. Xia, R. L. Arrowsmith, H. Ge, G. W. Nelson, J. S. Foord, M. Felipe-Sotelo, N. D. Evans, J. M. Mitchels and S. E. Flower, Hydrothermal conversion of one-photon-fluorescent poly (4-vinylpyridine) into two-photon- fluorescent carbon nanodots, Langmuir, 2014, 30, 11746-11752. 5. M. Li, H. Ge, R. L. Arrowsmith, V. Mirabello, S. W. Botchway, W. Zhu, S. I. Pascu and T. D. James, Ditopic boronic acid and imine-based naphthalimide fluorescence sensor for copper (II), Chem. Commun., 2014, 50, 11806-11809. 6. L. H. Davies, B. B. Kasten, P. D. Benny, R. L. Arrowsmith, H. Ge, S. I. Pascu, S. W. Botchway, W. Clegg, R. W. Harrington and L. J. Higham, Re and 99mTc complexes of BodP3–multi-modality imaging probes, Chem. Commun., 2014, 50, 15503-15505 II List of poster presented: List of poster presented: 1. H. Ge, Z. Hu, S. I. Pascu, S. W. Botchway, T. James, R. M. Tyrrell, New functional carbon cased nanomaterials for biomedical imaging applications, International conference on nanoscience and technology, ChinaNano 2013, 05th – 07th September 2013, Beijing, China. 2. H. Ge, Z. Hu, R. Arrowsmith, S. Flower, V. Mirabello. I. Pascu, S. W. Botchway, T. James, R. M. Tyrrell, hosted the RSC Macrocyclic and Supramolecular Chemistry Meeting, MASC 2013, 16th – 17th December 2013, University of Glasgow, Glasgow, UK. 3. M. Li, H. Ge, R. L. Arrowsmith, V. Mirabello, S. W. Botchway, W. Zhu, S. I. Pascu and T. D. James, Ditopic boronic acid and imine-based naphthalimide fluorescence sensor for Copper (II), Dalton Discussion 15: Metal ions in medical imaging: optical, radiopharmaceutical and MRI contrast, 8th –10th September 2014, University of York, York, UK. III Table of contents Table of Contents List of published articles during PhD ................................................................... II List of poster presented: ....................................................................................... III Abstract ............................................................................................................. VIII Acknowledgements ............................................................................................... X Abbreviations ..................................................................................................... XII Compounds list .................................................................................................. XV Chapter 1. Introduction .............................................................................................. 1 1.1. Aims of the project and context ................................................................... 1 1.2. Introduction to SWNTs: from synthesis and characterisation techniques 1.2.1. Carbon allotropes ..................................................................................... 8 1.2.2. Structure of SWNTs ............................................................................... 10 1.2.3. Synthesis of SWNTs .............................................................................. 12 1.2.4. Impurities typically found in as-made SWNT and their potential health and environment risks .......................................................................................... 22 1.2.5. Methods for the advanced purification of SWNTs for biomedical application ............................................................................................................ 25 1.2.6. Functionalisation methods for SWNTs .................................................. 27 1.2.7. Developments and applications of SWNTs in the biomedical field ...... 30 1.2.8. Characterisation techniques for SWNTs ................................................ 32 1.3. Introduction to fluorescence imaging and design of boronic acid- based fluorescence probes ................................................................................................ 42 1.3.1. Basics of fluorescence spectroscopies ................................................... 42 1.3.2. Jablonski energy diagram ...................................................................... 44 1.3.3. Important parameters in fluorescence: extinction coefficient, quantum yield and fluorescence lifetime ............................................................................ 47 1.3.4. Current design for fluorescence based sensor ........................................ 52 1.3.5. Design of biocompatible fluorescent sensors ........................................ 56 1.3.6. Applications of boronic acids as receptor molecules ............................. 58 1.3.7. Characterisation of fluorescence sensors ............................................... 61 1.4. Applications of SWNTs and their decoration with fluorescent taps in cancer research ....................................................................................................... 64 1.4.1. Introduction to cancer ............................................................................ 64 1.4.2. Applications of SWNTs in therapeutic drug delivery ............................ 65 1.4.3. Applications of SWNTs in cellular imaging .......................................... 68 IV Table of contents 1.4.4. Photothermal therapies mediated by the use of SWNTs ....................... 70 1.4.5. Photodynamic therapy (PDT) using SWNTs ......................................... 71 1.4.6. SWNTs-enhanced gene therapy ............................................................. 72 1.5. Specific objectives of this project .............................................................. 74 1.6. Reference for chapter one........................................................................... 75 Chapter 2. Synthesis and characterisation of fluorescent sensors ........................ 89 2.1. Overview ................................................................................................... 89 2.2. Optimisation of synthetic route. ................................................................ 90 2.3. Kinetic stability tests for fluorescent sensors .......................................... 105 2.4. Qualitative avidin binding tests for the fluorescence sensors .................. 109 2.5. Direct interaction between fluorescence sensor and purified SWNTs .... 110 2.6. Fluorescence titration of designed sensors .............................................. 111 2.7. Quantum yields of fluorescence sensors ................................................. 113 2.8. Summary of chapter two .......................................................................... 114 2.9. Reference for chapter two ........................................................................ 115 Chapter 3. Purification and characterisation