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Hybrid Silicon-Based Nanomaterials Synthesized Via Femtosecond Laser for Theranostics Applications

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Hybrid Silicon-Based Nanomaterials Synthesized Via Femtosecond Laser for Theranostics Applications HYBRID SILICON-BASED NANOMATERIALS SYNTHESIZED VIA FEMTOSECOND LASER FOR THERANOSTICS APPLICATIONS by Meysam Keshavarz Master of Science, University Technology of Malaysia (2012) Bachelor of Science, Esfahan Azad University (2010) A dissertation presented to Ryerson University in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the program of Aerospace Engineering Toronto, Ontario, Canada, 2017 © Meysam Keshavarz, 2017 AUTHOR’S DECLARATION FOR ELECTRONIC SUBMISSION OF A DISSERTATION I hereby declare that I am the sole author of this dissertation. This is a true copy of the dissertation, including any required final revision, as accepted by my examiners. I authorize Ryerson University to lend this dissertation to other institutions or individuals for the purpose of scholarly research. I further authorize Ryerson University to reproduce this dissertation by photocopying or by other means, in total or in part, at the request of other institutions or individuals for the purpose of scholarly research. I understand that my dissertation may be made electronically available to the public. ii HYBRID SILICON-BASED NANOMATERIALS SYNTHESIZED VIA FEMTOSECOND LASER FOR THERANOSTICS APPLICATIONS Meysam Keshavarz Doctor of Philosophy, Aerospace Engineering, Ryerson University, Toronto (2017) ABSTRACT Biocompatibility and bio-stability are two very important criteria of the materials being used in biology and biological related applications. Among biocompatible materials, Silicon has been widely used in biomedical applications such as logistic for drug delivery and scaffolds for tissue engineering. Therefore, Silicon is chosen to be further investigated in terms of its potential therapeutic and diagnostic applications. The main objective of this thesis is to explore capabilities of silicon-based nanomaterials on therapeutic and diagnostic of cancer HeLa and mammalian Fibroblast cell lines. The uniqueness of silicon-based nanomaterials synthesized in this study relies on utilization of femtosecond laser, a versatile yet precise method to generate nanoscale silicon- based materials. In the initial phase of this study, the need for manufacturing an alternative tool to modulate cells behavior is addressed. During this phase, it is shown that Induced Residual Stress (IRS) onto the Silicon chip via Ultrashort Pulsed Laser (USPL) irradiation is remarkably capable of remotely tuning cellular behavior by which the fate and directionality of seeded cells could be modulated. The second phase is dedicated to synthesis of a novel nanostructure to overcome the limitations of using Silicon-based bio-template for therapeutic applications. Thus far, Nano-scale silicon material has been employed in the form of either nanoparticles (NPs) or 3-D structure for drug delivery and scaffold respectively. Here, a self-assembled Silica Nano-web (SNW) that concurrently exhibits the therapeutic and proliferative attributions of NPs and 3-D structure is iii introduced. This SNW also demonstrates selective functionality by which mammalian cells and cancer cells are treated differently. The third phase of this study focuses on diagnostic applications of the silicon-based materials. In this phase, a label-free multiplex photoluminescent silicon nano-probe (PLSN-probe) as a potential substitute for quantum dots (QDs) in bioimaging is synthesized. An inherently non- photoluminescent silicon substrate is altered to create the PLSN-probe, which overcomes the major drawbacks of presently available QDs. The PLSN-probe not only demonstrates unique optical properties that can be utilized for bioimaging but also exhibits cell-selective uptake that allows the differentiation and diagnosis of HeLa and fibroblast cells. Last but not least, the final study is a unique approach of using polygonal Silicon quantum-probe (polygonal Si-QP) that utilizes a surface-enhanced Raman scattering (SERS) for diagnosis and differentiating of cancerous HeLa and fibroblast cells. It is demonstrated that the polygonal Si- QPs could be used for in-situ live cell analysis. Live Raman sensing has also exhibited promising outcome by which tracing of chemical transition in a cell could lead us to a better understanding of cellular changes. The obtained results indicate multifunctional feasibility of nano/quantum scale silicon based structures for therapeutic, bioimaging and diagnosis. The prospect applications of this thesis could lead to future studies and ultimately, new frontiers for universal cancer cell diagnosis. iv ACKNOWLEDGEMENTS First and foremost, would like to express my gratitude and appreciation for my supervisors Dr. Krishnan Venkatakrishnan and Dr. Bo Tan. It has been an honor to conduct my study under their supervision. I appreciate all the contributions of time, ideas, and funding to make my Ph.D. experience productive and stimulating. I would like to thank my committee members Dr. Z. Fawaz, Dr. P. Ouyang and Dr. S. Upreti for their valuable guidance and meticulous advices to shape the direction of my research project and refining my thesis. I would like to thank my parents. Words are unable to express the depth of my gratitude for their constant encouragement and support throughout the course of my entire academic career. I would also like to thank my sister Toktam for helping me whenever I needed any helps. Without them I could not have done this. v DEDICATION To my parents and my sister. vi TABLE OF CONTENTS ABSTRACT ............................................................................................................................................. iii DEDICATION ........................................................................................................................................ vi LIST OF FIGURES ................................................................................................................................. x LIST OF ABBREVIATIONS ............................................................................................................ xix CHAPTER 1 .............................................................................................................................................. 1 INTRODUCTION .................................................................................................................................... 1 1.1 Silicon as an ideal biocompatible materials .................................................................................... 1 1.2 Silicon based nanomaterials for biological applications ............................................................ 1 1.2.1 Nanostructured materials for tissue engineering ........................................................................................ 2 1.2.2 Conventional trends on synthesis of Silicon nano materilas .................................................................. 2 1.3 Regulation of cellular behavior ............................................................................................................ 4 1.4 Silicon Based Nanostructures for Cancer Therapy ........................................................................ 5 1.5 Silicon Nano-Probes for Diagnostic Bioimaging ............................................................................. 6 1.6 Silicon Quantum Probe towards Cancer Diagnosis ....................................................................... 8 1.7 Summary of the current limitations ................................................................................................... 8 1.8 Research Objective .................................................................................................................................... 9 1.8.1 To determine the interaction of cell-matter and modulation of cellular behavior ........................... 9 1.8.2 To synthesize polymorphic 3-D silica nanostructures .............................................................................. 9 1.8.3 To generate a multiplex PhotoLuminescent probe for cell-imaging and diagnosis ........................ 9 1.8.4 Fabrication of Raman sensitive probe for cancer diagnosis ................................................................... 9 1.9 Organization of thesis ........................................................................................................................... 10 CHAPTER 2 ........................................................................................................................................... 12 EXPERIMENTAL AND METHODS .............................................................................................. 12 2.1 Materials and methods ............................................................................................................................. 12 2.1.1 Experimental setup ............................................................................................................................................ 12 2.1.2 Laser induced functionalized stress component ....................................................................................... 12 2.1.3 Synthesis of Silicon Nano web ...................................................................................................................... 13 2.1.4 Synthesis of photoluminescence silicon nano probes ............................................................................. 13 2.1.5 Synthesis of the SERS-enabled polygonal Si-QPs .................................................................................. 13 2.2 Cell culture and seeding ..........................................................................................................................
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