Synthesis and Investigation of the Properties of Water Soluble Quantum Dots for Bioapplications
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Synthesis and Investigation of the Properties of Water Soluble Quantum Dots for Bioapplications A Thesis by Fatemeh Mir Najafi Zadeh Submitted in Partial Fulfilment of the Recruitment for the Degree of Doctor of Philosophy in Chemistry Supervisor: A/Prof. John A.Stride Co-supervisor: A/Prof. Marcus Cole School of Chemistry Faculty of Science August 2014 The University of New South Wales Thesis/ Dissertation Sheet Surname or family name: Mir Najafi Zadeh First name: Fatemeh Other name/s: Abbreviation for degree as given in the University calendar: PhD School: Chemistry Faculty: Science Title: Synthesis and Investigation of the Properties of Water Soluble Quantum Dots for Bioapplications Abstract Semiconductor nanocrystals or quantum dots (QDs) have received a great deal of attention over the last decade due to their unique optical and physical properties, classifying them as potential tools for biological and medical applications. However, there are some serious restrictions to the bioapplications of QDs such as water solubility, toxicity and photostability in biological environments for both in-vivo and in-vitro studies. In this thesis, studies have focused on the preparation of highly luminescent, water soluble and photostable QDs of low toxicity that can then be potentially used in a biological context. First, CdSe nanoparticles were synthesized in an aqueous route in order to investigate the parameters affecting formation of nanoparticles. Then, water soluble CdSe(S) and ZnSe(S) QDs were synthesized. These CdSe(S) QDs were also coated with ZnO and Fe2O3 to produce CdSe(S)/ZnO and CdSe(S)/Fe2O3 core/shell QDs. The cytotoxicities of as-prepared CdSe(S), ZnSe (S) and CdSe(S)/ZnO QDs were studied in the presence of two cell lines: HCT-116 cell line as cancer cells and WS1 cell line as normal cells. Finally, CdSe(S) QDs were linked to Donkey-anti mouse (H+L) (IgG) antibody Cy3 fluorophore to prepare a CdSe(S)-antibody conjugated compound and the photostability of CdSe(S) QDs both after linking to antibody and in the presence of HCT-116 cells was investigated. The obtained QDs exhibited high crystallinity, water solubility, low toxicity and photostability, demonstrating that highly crystalline nanoparticles can be formed by sufficient control of the experimental parameters. It was determined that coating the CdSe(S) QDs with ZnO led to a reduced cytotoxicity of the CdSe(S) QDs. It was found that ZnSe(S) QDs have no cytotoxicity toward both HCT-116 and WS1 cell lines across all concentrations studied. Finally, the CdSe(S) QDs were found to be photostable both in a CdSe(S)-antibody conjugated compound and in the presence of HCT-116 cancer cells. Declaration relating to disposition of project thesis/dissertation I hereby grant to the University of New South Wales or its agents the right to archive and to make available my thesis or dissertation in whole or in part in the University libraries in all forms of media, now or here after known, subject to the provisions of the Copyright Act 1968. I retain all property rights, such as patent rights. I also retain the right to use in future works (such as articles or books) all or part of this thesis or dissertation. I also authorise University Microfilms to use the 350 word abstract of my thesis in Dissertation Abstracts International. …………………………… ………………………...…… …………………….. Signature Witness Date The University recognises that there may be exceptional circumstances requiring restrictions on copying or conditions on use. Requests for restriction for a period of up to 2 years must be made in writing. Requests for a longer period of restriction may be considered in exceptional circumstances and require the approval of the Dean of Graduate Research. FOR OFFICE USE ONLY Date of completion of requirements for Award: i Certificate of Originality I hereby declare that this submission is my own work and to the best of my knowledge it contains no materials previously published or written by another person, nor material which to a substantial extent has been accepted for the award of any other degree or diploma at UNSW or any other educational institution, except where due acknowledgment is made in the thesis. Any contribution made to the research by others, with whom I have worked at UNSW or elsewhere, is explicitly acknowledged in the thesis. I also declare that the intellectual content of this thesis is the product of my own work, except to the extent that assistance from others in the project’s design and conception or in style, presentation and linguistic expression is acknowledged. Signed…………………………………… Date……………………………………… ii Copyright Statement I hereby grant the University of New South Wales or its agents the right to archive and to make available my thesis or dissertation in whole or part in the University libraries in all forms of media, now or here after known, subject to the provisions of the Copyright Act1968. I retain all proprietary rights, such as patent rights. I also retain the right to use in future works (such as articles or books) all or part of this thesis or dissertation. I also authorise University Microfilms to use the 350 word abstract of my thesis in Dissertation Abstract International. I have either used no substantial portions of copyright material in my thesis or I have obtained permission to use copyright material; where permission has not been granted I have applied/will apply for a partial restriction of the digital copy of my thesis or dissertation. Signed ........................................................... Date ................................................................. Authenticity Statement I certify that the Library deposit digital copy is a direct equivalent of the final officially approved version of my thesis. No emendation of content has occurred and if there are any minor variations in formatting, they are the result of the conversion to digital format. Signed ............................................................. Date ............................................................. iii Acknowledgments All praise and thanks goes to God who has created a unique order in everything, from the minuscule particles to magnificent universes. The years spent for PhD training was an excellent opportunity for me to be familiar with the fascinating world of nanoparticles, along with contacting with many people who assisted me to accomplish this research. I would like to express my gratitude to all of them. First and foremost, it is my absolute pleasure to thank my supervisor A/Prof. John Stride for teaching me many useful lessons and providing me with unlimited guidance and support to reach goals of my research. He has been so patient, encouraging, supportive and helpful in all of stages of this thesis and I am grateful to have worked with him. I would like to extend my special thanks to Dr. Deborah Ramesy and A/Prof. Shelly McAlpine for their kind collaboration about providing the cells and performing cytotoxicity assays. I would like to thank my co-supervisor, A/Prof. Marcus Cole and postgraduate coordinators of School of Chemistry, A/Prof. Jonathan Morris and Prof. Martina Stenzel for their kind cooperation, Prof. Brynn Hibbert for organizing Electronic Lab Notebook (ELN), Prof. Barbara Messerle and Prof. Scott Kable the heads of School of Chemistry for their great management and providing facilities. I am grateful to all the staff of School of Chemistry for assisting me, especially Ms. Lucy Stride, Mr. Ken McGuffin, Ms. Jodee Anning, Ms. Anne Ayres, Mr. Rick Chan, Mr. Steve Yonnoulatos, Mr. Ray Arnold, Dr. Tobby Jackson, Ms. Peta Di Bella, Dr. Route Devakaram, Mr. Rama Anning, Mr. Grant Platt and Dr. Doug Lawes. I am thankful to the staff of Mark Wainwright Analytical Centre of University of New South Wales for training me to use facilities: Dr. Yu Wang (XRD), Ms. Katie Levick and Dr. Aaron Dodd (TEM), Dr. Anne Rich (CD spectroscopy), Ms. Katerina Bendowa and Dr. Renee Wan (confocal microscopy). iv I would like to thank Dr. Fan Wang and Dr. Peter Reece for their kind assistance with photoluminescence spectroscopy and Dr. Bin Gong for performing XPS spectroscopy, Dr. Quadir Zakaria for his good comments about SAED, A/Prof. Grainne Moran for her useful guidance about CD spectroscopy, Mr. Stephan Parker for providing antibody, Mr. John Ronaldo, Mr. Teddy Chang and Dr. Michael Whittaker for their help about DLS and A/Prof. Ritha Khanna for her good advice. I gratefully acknowledge Australian Nanotechnology and Nano Science Network (ANN), Australian X-ray Analytical Association (AXAA) and Australian Microscopy Microanalysis Society (ACMM) for encouraging me with awarding several student bursaries to present my work, especially Ms.Liz Micallef, Dr.Vanessa Peterson, Prof. Chennuputi Jagadish, Prof. Ajayan Vinu, Prof. Jin Zou and Prof. Graeme Auchterlonie. I acknowledge all of my colleagues for their kind contribution: Fehmida, Mohammad, Arif, Tom, Trung, Maggi, Sanghun, Rob, Daniel, Roman, Mehandra, Boon, Madhuka, Rebecca, Eric and Jess. I would like to thank Mr.Abbas Barfidokht, Mr. Xiayn (Jet) Cheng, Mr. Adrian Plummer and Dr. Simone Ciampi for their good advice. I would also like to thank all of my former trainers and supervisors in University of Tehran and the University of Bu-Alisina of Hammadan. I am extremely thankful to Mrs. Anna Lumberou and her family who are the best friends for me and my family members. I am also grateful to all of my friends: Hamideh, Mitra, Roya, Maryam, Rima, Elham, Lida, Parisa and Leila for their kindness and support.