Engineering Nanoparticles for Biomedical Applications: From Theory to Experiments and Modelling

Practical approach to solution-based synthesis methods and mechanisms from a chemical engineering perspectives Engineering Nanoparticles for Biomedical Applications provides an in-depth, hands-on overview of synthesis and formation mechanisms, characterization, and functionalization of nanoparticles (NPs) using solution-based methods developed from fundamental principles of nucleation and growth. Various experimental synthesis strategies are supported via simulation and modeling. The NPs studied in this book are designed to target an array of biomedical applications. In this book, readers can practice reverse engineering by first choosing a specific biomedical application, upon which the reader will be exposed to a host of synthesis options. Based on desired properties of NPs, this book can then provide all the relevant information using modeling approaches for that specific biomedical application. Sample topics covered in Engineering Nanoparticles for Biomedical Applications include: Physico-chemical properties of NPs such as magnetic, plasmonic, and stimuli-sensitivity properties Modeling approaches including Density Functional Theory (DFT), Molecular Dynamics (MD), Monte Carlo simulations, and Population Balance Model Applications of NPs with emphasis on biomedical applications such as biosensing, diagnostics/imaging, and drug delivery Optical, magnetic, thermal, electrochemical, and biological properties of multifunctional nanoparticles Iron oxides in spherical magnetic NPs, detailing co-precipitation, thermal decomposition, and colloidal templating synthesis methods Engineering Nanoparticles for Biomedical Applications is an essential reference on the subject for chemists and engineers at every level of academia and industry.

Table of Contents:
Preface xvii Section I Synthesis and Characterization of Nanoparticles 1 1 Nucleation and Growth of Nanoparticles 3 Sulalit Bandyopadhyay and Seniz Ucar 1.1 Classical Nucleation Theory 4 1.2 Phase Stability and Phase Transformations 6 1.3 Crystal Growth 7 1.4 Control of Particle Size and Morphology 9 1.4.1 Control of Size and Size Distribution of Spherical NPs 9 1.4.1.1 Example 1: Spherical Iron Oxide NPs 11 1.4.1.2 Example 2: Spherical Au NPs 12 1.4.1.3 Example 3: Spherical Polymeric NPs 13 1.4.2 Control of Morphology of NPs 14 1.4.2.1 Example 1: Anisotropic Iron Oxide NPs 16 1.4.2.2 Example 2: Anisotropic Au NPs 17 1.5 Concluding Remarks 18 References 19 2 Characterization of Nanoparticles 23 Hammad Farooq and Haroon Zafar 2.1 Introduction 23 2.2 X-ray Diffraction (XRD) 24 2.3 Dynamic Light Scattering (DLS) 27 2.4 Nanoparticle Tracking Analysis (NTA) 29 2.5 Analytical Centrifuge (LUMiSizer) 33 2.6 Scanning Transmission Electron Microscopy (STEM) 36 2.7 Atomic Force Microscopy (AFM) 38 2.8 Fourier Transform Infrared (FT-IR) Spectroscopy 40 2.9 Raman Spectroscopy 41 2.10 Vibrating Sample Magnetometer 44 2.11 UV–Vis Spectroscopy 45 2.12 Selecting a Characterization Technique 47 References 48 3 Spherical Magnetic Nanoparticles 53 3.1 Magnetic Susceptibility 53 3.2 Magnetic Single-Domain Nanoparticles 56 3.3 Magnetic Anisotropy 57 3.4 Magnetic Interparticle Interactions 57 3.4.1 Exchange Interaction 57 3.4.2 Dipolar Interaction 58 3.4.3 RKKY Interaction 58 3.5 Characterizations of Magnetic Properties 59 3.5.1 Vibrating Sample Magnetometery (VSM) 59 3.5.2 Superconducting Quantum Interference Device (SQUID) 59 3.5.3 Magnetic Particle Spectroscopy 60 3.5.4 AC Susceptometry (ACS) 60 3.6 Iron Oxides 61 3.7 Synthesis Methods 62 3.7.1 Co-precipitation 62 3.7.2 Thermal Decomposition 66 3.7.3 Colloidal Templating 68 3.7.4 Other Methods 68 References 72 4 Anisotropic Magnetic Nanoparticles 77 Kingsley Poon, Jyotish Kumar, Janardhanan Saraswathy, Yogambha Ramaswamy, and Gurvinder Singh 4.1 Introduction 77 4.2 Synthesis of Anisotropic Magnetic Nanoparticles 78 4.2.1 Thermal Decomposition 79 4.2.2 Co-precipitation 83 4.2.3 Hydrothermal 83 4.3 Magnetic Properties of Anisotropic Nanoparticles 85 4.4 Biomedical Applications of Anisotropic Magnetic Nanoparticles 88 4.4.1 Anisotropic Magnetic Nanoparticles for MRI Contrast Agent 88 4.4.2 Anisotropic Magnetic Nanoparticles for Magnetic Hyperthermia 92 4.5 Summary 96 References 97 5 Size Selective Synthesis of Spherical Gold Nanoparticles 101 Avijit Mondal and Nikhil R. Jana 5.1 Introduction 101 5.2 Formation Mechanism of Au NP via Colloid Chemistry Approach 102 5.2.1 Au NP of 1–5nm Size Using Strong Capping Ligands 105 5.2.2 Au NP in the Size Range of 5–200nm via Seeding Growth 106 5.2.3 Au NP of 5–100nm by Controlling Nucleation-Growth Kinetics 110 5.2.4 Au NPs in the Size Range of 1–15 nm via Ostwald/Digestive Ripening Approach 113 5.3 Controlling Au NP Size Distribution 114 5.4 Conclusions and Future Aspect 115 References 116 6 Anisotropic Plasmonic Nanostructures 125 Neethu Thomas and Soumodeep Biswas 6.1 Introduction 125 6.2 Optical Properties of Plasmonic Nanostructures 126 6.2.1 Theory of Surface Plasmon Resonance 126 6.2.2 LSPR Through Mie and Mie–Gans Theory 127 6.2.3 Tuning of LSPR Through Size and Shape of Metal Nanostructures 129 6.3 Evolution of Shape Anisotropy 130 6.3.1 General Classifications of Nanostructures 130 6.3.2 Nuclei to Seed Transition 131 6.3.3 Shapes from Single-Crystalline Seeds 131 6.3.4 Shapes from Singly Twinned, Multiply Twinned Seeds, and Seeds with Stacking Faults (Zone II to V) 131 6.4 The Kinetic and Thermodynamic Control for Shape Anisotropy 133 6.4.1 Symmetry Breaking of Seeds 134 6.4.2 Kinetic Aspects in Evolution of Shape Anisotropy 135 6.4.3 Thermodynamic Aspects in Evolution of Shape Anisotropy 136 6.4.4 Competing Kinetics and Thermodynamics in Anisotropic Growth 136 6.5 Wet Chemical Synthesis and Related Mechanism of Au Nanostructures 138 6.6 Summary 139 References 140 7 Polymeric Nanoparticles 145 Leonardo Caserio, Vladimir Matining, Camillo Colli, Emanuele Mauri, and Davide Moscatelli 7.1 Introduction 145 7.2 Properties of PNPs 146 7.3 Stimuli-Sensitive PNPs 150 7.3.1 pH-Responsive Polymers and PNPs 150 7.3.2 Redox-Responsive Polymers and PNPs 153 7.3.3 Ultrasound-Responsive Polymers and PNPs 154 7.3.4 Light-Responsive Polymers and PNPs 155 7.3.5 Temperature-Responsive Polymers and PNPs 156 7.4 Polymerization Techniques 159 7.4.1 ROP 159 7.4.2 RAFT Polymerization 159 7.4.3 ATRP 162 7.4.4 Emulsion Polymerization and Self-assembly 163 7.5 Biocompatible PNPs via Nanoprecipitation Strategies 165 7.5.1 Nanoprecipitation 165 7.5.2 Flash Nanoprecipitation 169 7.6 Conclusions 173 References 174 8 Multifunctional Nanoparticles 187 Gisela Luz 8.1 Introduction 187 8.2 What Are Multifunctional Nanoparticles? 187 8.3 Properties of Multifunctional NPs and Their Applications 190 8.3.1 Physicochemical Properties 191 8.3.1.1 Optical Properties 191 8.3.1.2 Magnetic Properties 192 8.3.1.3 Thermal Properties 194 8.3.1.4 Electrochemical Properties 196 8.3.2 Biological Properties 197 8.3.2.1 Biocompatibility and Toxicity 197 8.3.2.2 Targeting Ability 198 8.3.2.3 Biodegradability 199 8.3.2.4 Immunogenicity 200 8.4 Synthesis Methods and Formation Mechanisms 200 8.4.1 Bimetallic Nanoparticles 201 8.4.1.1 Physical Synthesis Methods 203 8.4.1.2 Chemical Synthesis Methods 204 8.4.1.3 Biological Synthesis Methods 208 8.4.2 Polymer–Metal NPs 208 8.4.2.1 Hydrogel–Metal Nanoparticles 212 8.5 Final Considerations 212 References 213 Section II Modeling Approaches for Synthesis of Nanoparticles 221 9 Overview of Modeling Approaches for Nanoparticle Synthesis in Liquid Phase 223 Puneet Koli and Rajdip Bandyopadhyaya 9.1 Introduction 223 9.1.1 Need for Modeling Approaches 224 9.2 Modeling Approaches for Studying Nanoparticle Formation Behavior 224 9.2.1 First-Principle Quantum Mechanical Models 224 9.2.1.1 Hartree–Fock Method 224 9.2.1.2 Hohenberg–Kohn and Kohn–Sham Formulations 225 9.2.1.3 Some Relevant Applications 226 9.2.2 Monte Carlo Simulations 228 9.2.2.1 Metropolis Monte Carlo Method 229 9.2.2.2 General Algorithm 229 9.2.2.3 Some Relevant Applications 230 9.2.3 Molecular Dynamics Simulations 233 9.2.3.1 General Algorithm 233 9.2.3.2 Some Relevant Applications 234 9.2.4 Population Balance Modeling 239 9.2.4.1 One-dimensional Population Balance Model 239 9.2.4.2 Some Relevant Applications 240 9.2.5 Mesoscale Models 241 9.2.5.1 Langevin Dynamics or Brownian Dynamics 241 9.2.5.2 Dissipative Particle Dynamics 242 9.2.5.3 Multiparticle Collision Dynamics 242 9.2.5.4 Lattice Boltzmann Method 242 9.3 Conclusions 243 References 244 10 Mechanistic Understanding of Nanoparticle Growth Using Density Functional Theory 247 Bratin Kumar Das and Ethayaraja Mani 10.1 Introduction 247 10.2 Quantum Mechanical Theory 248 10.2.1 The SchrodingerWave Equation 248 10.2.2 Density Functional Theory 249 10.3 Applications of DFT in Nanoparticle Growth 251 10.4 Conclusions 255 References 256 11 Molecular Dynamics (MD) 259 Miteshkumar Moirangthem, Kush Kumar, and Santosh Kumar Meena 11.1 Introduction to Basic Concepts in MD 259 11.1.1 Equations of Motion 260 11.1.2 Integration of the Equation of Motion 261 11.1.3 Ensembles 262 11.1.4 Interaction Potentials 263 11.1.5 Cutoff Scheme and Treatment of Long-range Interactions 264 11.1.6 Periodic Boundary Conditions 265 11.1.7 Forcefield Parameters 265 11.1.8 Deriving New Parameters 265 11.1.9 Analysis 266 11.2 Scope of MD in Understanding the Formation Mechanisms of Anisotropic Nanoparticles and Their Surface Properties 266 11.3 Understanding the Shape Control of Gold Nanorod Using MD Simulations 267 11.3.1 Model and Simulation Details 267 11.3.2 Results and Discussion 270 11.3.2.1 Role of Surfactant 270 11.3.2.2 Role of Geometry of Nanoseed 274 11.3.2.3 Role of Halide Ions 275 11.3.2.4 Role of Silver Ions 279 11.3.2.5 Inclusion of Metal Surface Polarization Effect in Simulation Models 281 11.3.3 Conclusions 284 References 286 12 Kinetic Monte Carlo Simulation of Nanoparticle Growth 291 Remya Ann Mathews Kalapurakal and Ethayaraja Mani 12.1 Introduction 291 12.2 Theory of Jump Markov Processes 292 12.3 kMC Simulation of Nanoparticle Formation 295 12.3.1 kMC Simulation of Pure Aggregation 295 12.3.2 kMC Simulation of Nucleation and Growth Processes 296 12.3.3 kMC Simulation of Reaction and Molecular Growth 298 12.3.4 kMC Simulation of Ostwald Ripening 299 12.3.5 kMC Simulation of Nucleation, Growth, and Aggregation 301 12.3.6 kMC Simulation of Nanoparticle Formation in Reverse Micelles 302 References 308 13 Modeling of Nanoparticle Formation Using Population Balance Equation 313 Sriram Krishnamurthy and Ethayaraja Mani 13.1 Introduction 313 13.2 Population Balance Equation 314 13.2.1 Analytical Solution of PBE 315 13.2.1.1 Pure Growth 315 13.2.1.2 Nucleation and Growth 316 13.2.1.3 Pure Aggregation 316 13.3 Nanoparticle Formation 317 13.3.1 PBM of Pure Aggregation 317 13.3.2 PBM of Reaction, Nucleation, and Growth 321 13.3.3 Mechanism-enabled PBM of Formation of Nanoparticles 323 13.3.4 Effect of Mixing on the Formation of Nanoparticles 324 13.3.5 PBM of Nanoparticle Formation in Swollen Reverse Micelles (RM) 326 13.4 Conclusion 329 13.A Numerical Solution of PBE 329 13.A.1 Moment Methods 329 13.A.2 Sectional Methods 330 13.A.3 Stochastic Methods 330 References 331 Section III Applications of Nanoparticles in Biomedicine 335 14 Emerging Trends in Optical and Magnetic Sensing for Biomolecular Detection 337 Homa Hassan, Shrishti Kumari, Sriram Rathnakumar, E. T. Athira, Mayilvahanan Bose, V. V. R. Sai, Narayanan Madaboosi, and Jitendra Satija 14.1 Introduction 337 14.2 Optical Biosensors 338 14.2.1 Colorimetric Biosensors 338 14.2.2 Fluorescent Biosensors 340 14.2.3 Surface-Enhanced Raman Scattering (SERS) Biosensors 344 14.2.4 Surface Plasmon Resonance and Localized SPR Biosensors 346 14.2.5 EvanescentWave Biosensors 348 14.3 Magnetic Biosensors 351 14.3.1 Magnetic Nanoparticles 351 14.3.1.1 Magnetic Nanoparticles – Synthesis, Characterization and Properties 351 14.3.2 Magnetic Sensors 354 14.3.2.1 Superconducting Quantum Interference Devices (SQUID) 354 14.3.2.2 Hall Effect Sensors 355 14.3.2.3 Magnetoresistive Magnetometers 356 14.3.3 Magnetic Nanoparticles for Sample Preparation and Bioassays 359 14.3.4 Non-microfluidic MNPs for Biosensing 360 14.3.5 MNPs for Microfluidic Sample Preparation and Enrichment 362 14.3.6 MNPs for Signal Transduction in Microfluidic Sensing 363 14.4 Summary and Future Perspectives 364 References 365 15 Nanoparticles in Imaging and Diagnostics 377 Sofie Snipstad and Catharina de Lange Davies 15.1 Introduction 377 15.2 Imaging Techniques 377 15.2.1 MRI 377 15.2.1.1 Principle 377 15.2.1.2 Contrast Agents 378 15.2.1.3 Application 378 15.2.2 CT 379 15.2.2.1 Principle 379 15.2.2.2 Contrast Agents 379 15.2.2.3 Application 380 15.2.3 PET 380 15.2.3.1 Principles 380 15.2.3.2 Radioisotopes 381 15.2.3.3 Application 381 15.2.4 SPECT 382 15.2.4.1 Principles 382 15.2.4.2 Radioisotopes 382 15.2.4.3 Application 382 15.2.5 US Imaging 382 15.2.5.1 Principle 382 15.2.5.2 Contrast Agents 383 15.2.5.3 Application 383 15.2.6 Photoacoustic Imaging 384 15.2.6.1 Principle 384 15.2.6.2 Contrast Agents 384 15.2.6.3 Application 384 15.2.7 Optical Imaging 384 15.2.7.1 Principle 384 15.2.7.2 Contrast Agents 385 15.2.7.3 Application 385 15.3 Advantages and Disadvantages of the Various Imaging Modalities 386 15.3.1 Labeling of Nanoparticles 387 15.4 Combining Imaging Modalities 387 15.5 Ex Vivo Imaging 389 References 389 16 Drug Delivery Using Nanocarriers 395 Catharina de Lange Davies and Sofie Snipstad 16.1 Barriers for Delivery of Nanoparticles 395 16.1.1 Nanoparticles in the Blood 395 16.1.2 Transport Process: Convection and Diffusion 397 16.1.3 Extravasation of NPs Across the CapillaryWall 398 16.1.4 Penetration of NPs Through the Interstitial Space 399 16.2 Cellular Uptake and Intracellular Trafficking 400 16.3 Active–Passive Targeting 401 16.4 Applications in Disease Treatment 402 16.4.1 Cancer 402 16.4.2 Neurogenerative Diseases 405 16.4.3 Immunotherapy 406 16.4.4 Gene Therapy 407 16.4.5 Inflammatory Diseases 407 16.4.6 Cardiovascular Diseases 407 16.5 Improving Delivery of NPs 408 16.5.1 Remodeling the Tumor Microenvironment 408 16.5.2 Ultrasound-mediated Drug Delivery 408 16.6 Conclusion 410 Acknowledgement 410 References 410 Index 423

About the Author :
Sulalit Bandyopadhyay is an Associate Professor for Particle Engineering and Hydrometallurgy in the Department of Chemical Engineering, NTNU. He is also a Researcher at the Department of Water Management, TU Delft, Netherlands and serving as the CTO of a diagnostic company Lybe Scientific A/S. Trained as a chemical engineer, he specializes in the field of colloids, polymers, and nanomaterials with an overall interest in tailoring particles towards specific applications in the field of nanomedicine.