Dr. Bin Liu is the Provost's Chair Professor and Head of Department of Chemical and Biomolecular Engineering, National University of Singapore (NUS), Singapore. She received her PhD degree from NUS and started her independent academic career after a postdoctoral training at the University of California, Santa Barbara, USA. She has authored and co-authored over 350 scientific publications. Named among the World's Most Influential Minds and the Top 1% Highly Cited Researchers in Materials Science by Thomson Reuters and Clarivate Analytics from 2014 to 2017, Dr. Liu specializes in bringing organic soluble materials into aqueous media, with a focus on the exploration of their unique applications in biomedical research, environmental monitoring and electronic devices. Dr. Liu is the recipient of multiple prestigious awards, including the National Science and Technology Young Scientist Award, L'Oreal Women in Science National Fellowship, Asia Rising Star, Singapore National Institute of Chemistry-BASF Materials Award, Singapore National Research Foundation lnvestigatorship, Elsevier Materials in Society Lectureship, NUS Provost's Chair Professorship and the President's Technology Award. She was also recently elected as a Fellow of the Royal Society of Chemistry, Fellow of Singapore Academy of Engineering and Asia-Pacific Academy of Materials, in addition to multiple invitations to serve on the editorial boards of 15 international refereed journals. Besides her academic endeavors, Dr. Liu is highly active in technopreneurship. She holds 28 patents, of which 15 have been licensed to companies across the US, UK and Asia, and co-founded a start-up company Luminicell to commercialize her bioprobe technology based on fluorogens with aggregation-induced emission feature.

Preface xi

1 Strategies to Bring Conjugated Polymers into Aqueous Media 1Jie Liu and Bin Liu

1.1 Introduction 1

1.2 Synthesis of CPEs 2

1.2.1 Anionic CPEs 4

1.2.1.1 Sulfonated CPEs 4

1.2.1.2 Carboxylated CPEs 8

1.2.1.3 Phosphonated CPEs 13

1.2.2 Cationic CPEs 14

1.2.2.1 Ammonium CPEs 14

1.2.2.2 Pyridinium CPEs 20

1.2.2.3 Phosphonium CPEs 21

1.2.3 Zwitterionic CPEs 21

1.3 Neutral WSCPs 23

1.4 Fabrication of CPNPs 25

1.4.1 Reprecipitation 26

1.4.2 Miniemulsion 26

1.4.3 Nanoprecipitation 28

1.5 Conclusion 30

References 30

2 Direct Synthesis of Conjugated Polymer Nanoparticles 35Sibel Ciftci and Alexander J. C. Kuehne

2.1 Introduction 35

2.2 Generation of CPNs 39

2.2.1 Postpolymerization Techniques 39

2.2.1.1 Nanoprecipitation 39

2.2.1.2 Miniemulsification 41

2.2.1.3 Microfluidics 42

2.2.1.4 Self?]Assembly 45

2.2.2 Direct Polymerization in Heterogeneous Systems 45

2.2.2.1 Emulsion Polymerization 46

2.2.2.2 Polymerization in Miniemulsion 48

2.2.2.3 Polymerization in Microemulsion 49

2.2.2.4 Dispersion Polymerization 50

2.3 Conclusion 53

References 53

3 Conjugated Polymer Nanoparticles and Semiconducting Polymer Dots for Molecular Sensing and InVivo and Cellular Imaging 59Xu Wu and Daniel T. Chiu

3.1 Introduction 59

3.2 Preparation, Characterization, and Functionalization 60

3.2.1 Preparation 60

3.2.2 Characterization 61

3.2.3 Functionalization 62

3.3 Molecular Sensing 65

3.3.1 Metal?]Ion Sensing 65

3.3.2 Oxygen and Reactive Oxygen Species Detection 66

3.3.3 pH and Temperature Monitoring 69

3.3.4 Sensing of Other Molecules 71

3.4 Cellular Imaging 74

3.4.1 Fluorescence Imaging 74

3.4.1.1 In Vitro Imaging 74

3.4.1.2 In Vivo Imaging 76

3.4.2 Photoacoustic Imaging 77

3.4.3 Multimodality Imaging 77

3.5 Conclusion 80

Acknowledgment 81

References 81

4 Conjugated Polymers for In Vivo Fluorescence Imaging 87Jun Li and Dan Ding

4.1 Introduction 87

4.2 In Vivo Fluorescence Imaging of Tumors 88

4.3 Stimuli?]Responsive Fluorescence Imaging 92

4.4 In Vivo Fluorescence Cell Tracking 95

4.5 Two?]Photon Excited Brain Vascular Imaging 98

4.6 Dual?]Modality Imaging of Tumors In Vivo 99

4.7 Other In Vivo Fluorescence Imaging Applications 101

4.8 Conclusions and Perspectives 103

References 103

5 -Conjugated/Semiconducting Polymer Nanoparticles for Photoacoustic Imaging 111Chen Xie and Kanyi Pu

5.1 Introduction 111

5.2 Mechanism of PA Imaging 112

5.3 SPNs for PA Imaging 114

5.3.1 Preparation of SPNs 114

5.3.2 PA Imaging of Brain Vasculature 116

5.3.3 PA Imaging of Tumor 119

5.3.4 PA Imaging of Lymph Nodes 123

5.3.5 PA Imaging of ROS 125

5.3.6 Multimodal Imaging 125

5.4 Summary and Outlook 127

References 129

6 Conjugated Polymers for Two?]Photon Live Cell Imaging 135Shuang Li, Xiao?]Fang Jiang, and Qing?]Hua Xu

6.1 Introduction 135

6.2 Conjugated Polymers and CPNs as One?]Photon Excitation Imaging Contrast Agents 138

6.3 Conjugated Polymers as 2PEM Contrast Agents 140

6.4 Conjugated?]Polymer?]Based Nanoparticles (CPNs) as 2PEM Contrast Agents 146

6.4.1 CPNs Prepared from Hydrophobic Conjugated Polymers 146

6.4.2 CPNs Prepared from Conjugated Polyelectrolytes (CPEs) 150

6.4.3 CPNs Prepared by Hybrid Materials 152

6.5 Conclusions and Outlook 158

References 160

7 Water?]Soluble Conjugated Polymers for Sensing and Imaging Applications 171Xingfen Liu, Wei Huang, and Quli Fan

7.1 Introduction 171

7.2 Conjugated Polymers for Sensing 172

7.2.1 Sensing Based on FRET 172

7.2.1.1 One?]Step FRET 172

7.2.1.2 Two?]Step FRET 177

7.2.2 Sensing Based on Superquenching of CPs 178

7.2.2.1 Analytes?]Induced Quenching 178

7.2.2.2 Gold Nanoparticles?]Induced Superquenching 180

7.2.2.3 Graphene Oxide?]Induced Superquenching 183

7.2.3 Sensing Based on Conformation Conversion 183

7.2.4 Sensing Based on Aggregation of Conjugated Polymers 185

7.3 Imaging of Conjugated Polymers 186

7.3.1 Single?]Modal Imaging 188

7.3.1.1 Fluorescence Imaging 188

7.3.1.2 Far?]Red and NIR Imaging 190

7.3.1.3 Two?]Photon Imaging 193

7.3.1.4 Multicolor Imaging 196

7.3.2 MultiModal Imaging 201

7.3.2.1 MRI/Fluorescence Imaging 201

7.3.2.2 Fluorescence/Dark?]Field Imaging 206

7.3.2.3 MRI/Photoacoustic Imaging 209

7.4 Challenges and Outlook 209

References 210

8 Conjugated Polymers for Gene Delivery 215Joong Ho Moon and Kenry

8.1 Introduction 215

8.2 Fundamental Properties of Conjugated Polymers 216

8.3 Intracellular Targeting, Cytotoxicity, and Biodegradability of Conjugated Polymers 218

8.4 Plasmid DNA (pDNA) Delivery 222

8.5 Small Interfering RNA (siRNA) Delivery 226

8.6 Conclusions and Outlook 232

References 234

9 Conductive Polymer?]Based Functional Structures for Neural Therapeutic Applications 243Kenry and Bin Liu

9.1 Introduction 243

9.2 Conductive Polymer?]Based Functional Structures 244

9.2.1 Conductive Polymers 244

9.2.2 Conductive Polymer?]Based Hydrogels 249

9.2.3 Conductive Polymer?]Based Nanofibers 250

9.3 Synthesis and Functionalization of Conductive Polymer?]Based Functional Structures 251

9.3.1 Synthesis and Doping of Conductive Polymers 251

9.3.2 Fabrication of Electroconductive Hydrogels 252

9.3.3 Electrospinning of Conductive Polymer?]Based Nanofibers 253

9.3.4 Functionalization and Modification of Conductive Polymer?]Based Functional Structures 254

9.4 Applications of Conductive Polymer?]Based Functional Structures for Neural Therapies 255

9.4.1 Electrostimulated Drug Delivery 255

9.4.2 Neural Cell and Tissue Scaffolds for Neural Regeneration 257

9.4.3 Implantable Biosensors and Neural Prostheses 258

9.5 Summary and Outlook 260

References 261

10 Conjugated Polymers for Photodynamic Therapy 269Thangaraj Senthilkumar and Shu Wang

10.1 Introduction 269

10.1.1 Photodynamic Therapy Concept and History 269

10.1.2 Outline of the PDT Process 269

10.1.3 Role of Conjugated Polymers in PDT 271

10.1.4 Photochemistry Behind the PDT Process 271

10.1.5 Design Aspects of Effective PDT 272

10.2 Conjugated Polymers as Photosensitizers 274

10.2.1 Far?]Red/Near?]IR Emitting CP as Photosensitizers 274

10.2.2 CP as Energy Transfer Systems to Photosensitizing Dyes 274

10.2.3 Hybrid Photosensitizers based on CP 277

10.3 Applications of CP?]Based Photodynamic Therapy 277

10.3.1 Antimicroorganism Activity 277

10.3.2 Antitumor Therapy 285

10.4 Conclusions and Future Perspectives 291

References 291

11 Conjugated Polymers for Near?]Infrared Photothermal Therapy of Cancer 295Ligeng Xu, Xuejiao Song, and Zhuang Liu

11.1 Introduction 295

11.2 Conjugated Polymers for Cancer Photothermal Therapy 295

11.2.1 Polyaniline (PANI) Nanoparticles 296

11.2.2 Polypyrrole (PPy) Nanoparticles 297

11.2.3 PEDOT:PSSPEG Nanoparticles 298

11.2.4 DonorAcceptor (DA) Conjugated Polymers 299

11.3 Imaging Guided Photothermal Therapy 301

11.4 Conjugated Polymers for Combination Cancer Treatment 306

11.4.1 Combined Photodynamic and Photothermal Therapy 307

11.4.2 Combined Photothermal Chemotherapy 309

11.5 Outlook and Perspectives 312

References 316

12 Conjugated Polymers for Disease Diagnosis and Theranostics Medicine 321Akhtar Hussain Malik, Sameer Hussain, Sayan Roy Chowdhury, and Parameswar Krishnan Iyer

12.1 Introduction 321

12.2 Disease Diagnostics via Conjugated Polymers 322

12.2.1 Detection of Pathogens (E. coli, C. albicans, B. subtilis) 322

12.2.2 Detection of Cancer Biomarkers (DNA Methylation, miRNAs, Hyaluronidase, Spermine) 327

12.2.2.1 DNA Methylation 329

12.2.2.2 MicroRNAs (miRNA) Detection 333

12.2.2.3 Hyaluronidase (HAase) Detection 335

12.2.2.4 Spermine Detection 335

12.2.3 Detection of Other Important Biomarkers

(Acid Phosphatase, Bilirubin) 337

12.2.3.1 Acid Phosphatase (ACP) Detection 337

12.2.3.2 Bilirubin Detection 338

12.3 Conjugated Polymers for Cancer Theranostics 340

12.3.1 Photodynamic Therapy (PDT) 340

12.3.2 Photothermal Therapy (PTT) 342

12.4 Studying Neurodegenerative Disorders 345

12.4.1 Diagnostics via Conjugated Polymers 345

12.4.2 Therapeutic Strategies to Prevent Neurodegenerative Disorders 351

References 355

13 Polymer?]Grafted Conjugated Polymers as Functional Biointerfaces 359Alissa J. Hackett, Lisa T. Strover, Paul Baek, Jenny Malmström, and Jadranka Travas?]Sejdic

13.1 Introduction 359

13.2 Methods of Functionalizing CPs 361

13.2.1 Biodopants 361

13.2.2 Biomolecule Attachment 361

13.2.3 Copolymers and Polymer Blends 361

13.3 CP?]Based Polymer Brushes as Biointerfaces: Rationale and Applications 362

13.3.1 Antifouling 362

13.3.2 Biosensing 365

13.3.3 Tissue Engineering 366

13.3.4 Stimuli?]Responsive Materials 367

13.3.5 Emerging Bioelectronics Materials Based on Grafted CPs 372

13.4 Synthesis of CP?]Based Graft Copolymer Brushes 372

13.4.1 Grafted CPs: Synthesis by Grafting Through Approach 374

13.4.2 Grafted CPs: Synthesis by Grafting To Approach 377

13.4.3 Grafted CPs: Synthesis by Grafting From Approach 378

13.5 Conclusions and Outlook 385

References 387

Index 403