Bio-Nanomedicine for Cancer Therapy (Advances in Experimental Medicine and Biology Book 1295)

The book covers the latest developments in biologically-inspired and derived nanomedicine for cancer therapy. The purpose of the book is to illustrate the significance of naturally-mimicking systems for enhancing the dose delivered to the tumor, to improve stability, and prolong the circulation time. Moreover, readers are presented with advanced materials such as adjuvants for immunostimulation in cancer vaccines. The book also provides a comprehensive overview of the current status of academic research. This is an ideal book for students, researchers, and professors working in nanotechnology, cancer, targeted drug delivery, controlled drug release, materials science, and biomaterials as well as companies developing cancer immunotherapy. Preface Contents Part I: 101 Ways on Conventional Nanotherapies and How to Spice It Up Conventional Nanosized Drug Delivery Systems for Cancer Applications 1 DDSs Enhancing the Therapeutic Effects of Co-delivered Drugs in Cancer Treatment 2 Lipid-Based NCs 3 Metallic and Nonmetallic NPs, Nanoshells, Nanorattles, and QDs 4 Fullerenes, NTs and Carbon Nanostructures 5 Monodisperse Nanocrystals and Close-Packed Nanocrystal Assemblies 6 Dendrimers and Hyperbranched Polymers 7 Emulsions and Micelles 8 Drug Targeting Strategies 9 Passive Targeting 9.1 Size and Shape 9.2 pH 9.3 Temperature 10 Active Targeting 10.1 Peptides and Proteins 10.2 Aptamers 10.3 Other Molecules 11 Combined Targeting 11.1 Anticancer Nanosized DDSs on Market 12 Efficacy and Side Effects 13 Physicochemical Properties 13.1 Size and Shape 13.2 Surface Chemistry 14 Health Costs of DDSs in Cancer Therapy 15 Receptors 16 Transporters 17 Enzymes 18 Antibodies 19 Hybrid DDSs 20 Future Perspectives and Conclusions Bibliographic Database Search (Carried Out on March 22, 2019 at 12:30 AM) Boolean/Proximity Operators and Wildcard Characters General Database Settings Manuscript Selection References Homing Peptides for Cancer Therapy 1 Introduction 1.1 Next-Generation Cancer Therapies 1.1.1 Immunotherapy 1.1.2 Personalized Molecular Therapies 1.1.3 Nanomedicine 1.2 Active Cancer Targeting with Affinity Ligands 1.2.1 Tumor-Homing Peptides 2 Vascular Heterogeneity and Homing Peptide Discovery 2.1 Vascular Zip Codes 2.2 Peptide Phage Display 2.2.1 In Vitro Biopanning for Homing Peptide Detection 2.2.2 Agnostic In Vivo Peptide Phage Biopanning 2.3 Docking-Based Tumor Homing Peptides 2.3.1 Integrin-Targeting Homing Peptides 2.3.2 Aminopeptidase N Targeting Homing Peptides 2.3.3 P32/qC1qR Targeting 2.3.4 Homing Peptides for Targeting Fibrin–Fibronectin Complexes 2.3.5 Homing Peptides for Stage-Specific Tumor Targeting 2.3.6 Malignant Extracellular Matrix Targeting Peptides 2.3.7 Hyaluronan Targeting Peptides 2.3.8 Tumor-Associated Macrophage Targeting Peptides 2.3.9 Nucleolin Targeting Peptides 2.3.10 Epidermal Growth Factor Receptor Targeting Peptide 2.4 Tumor-Penetrating Peptides 2.4.1 Novel Tumor-Penetrating Peptides 2.4.2 Translational Development and Perspectives of TPP Technology 3 Conclusions and Perspectives References Radiolabeling of Theranostic Nanosystems 1 Introduction 2 Key Concepts in Radiochemistry for Theranostic Nanosystem Development 2.1 Radioactive Decay and Properties of Radiolabeled Tracers 2.2 Nuclear Reactions for Radionuclide Production 2.3 Principles for the Safe Handling of Radioactive Materials 2.4 Radiometric Detection Methods and Nuclear Imaging 3 Radiolabeling Strategies 3.1 Radiometals 3.1.1 Chelator-Mediated Radiolabeling with Radiometals 3.1.2 Chelator-Free Radiolabeling 3.2 Radiohalogenation 3.3 Radiolabeling with Positron-Emitting Radionuclides 3.4 Pretargeted Radiolabeling Strategies 3.5 Radiolabeling with Alpha Emitters 4 Preclinical Studies with Radiolabeled Tracers 4.1 In Vitro Methods 4.1.1 Radiolabel Stability Assays 4.1.2 Cell Uptake and Internalization Assays 4.1.3 Markers for Radiation-Induced Cellular Damage 4.2 Ex Vivo Biodistribution Studies and Autoradiography 4.3 Small Animal PET and SPECT/CT Imaging Studies 4.4 Radiotherapy Studies and Dosimetry 5 Current Examples of Radiolabeled Theranostic Nanosystems 6 Conclusion References Boosting Nanomedicine Efficacy with Hyperbaric Oxygen Therapy 1 Introduction 2 Hyperbaric Oxygen Therapy 2.1 Principle of HBO Therapy 2.2 Side Effects of HBO Therapy 2.3 Comparison Between HBO and Other Strategies in Overcoming Tumor Hypoxia 2.4 Applications of HBO Therapy in Cancer Therapies 2.4.1 Application of HBO in Radiotherapy 2.4.2 Application of HBO in Chemotherapy 2.4.3 Application of HBO in Photodynamic Therapy (PDT) 3 Potentiating Nanomedicine Antitumor Efficacy with HBO 4 Summary and Perspectives References Part II: Shuffle It Up with Innovative Treatment Modalities Mesoporous Silica Nanoparticles as Carriers for Biomolecules in Cancer Therapy 1 Introduction 2 Synthesis of MSNs 2.1 Large-Pore MSNs for Macromolecular Drugs 3 Gatekeepers for Controlled Drug Release 3.1 External Stimuli 3.1.1 Magnetic Field 3.1.2 Photodynamic Therapy 3.1.3 Ultrasound 3.2 Internal Stimuli 3.2.1 Release Based on pH 3.2.2 Release Based on Glutathione 3.2.3 Release Based on Biomolecular Recognition 4 Macromolecular Drug Delivery by MSNs for Cancer Diagnosis and Therapy 4.1 Peptide/Protein Delivery 4.2 Gene Delivery 4.2.1 pDNA Delivery 4.2.2 Aptamers for Targeted Delivery of MSNs 4.2.3 siRNA Delivery 4.2.4 MicroRNA Delivery 5 MSNs for Cancer Immunotherapy 6 Conclusions and Future Perspectives References Clearable Nanoparticles for Cancer Photothermal Therapy 1 Introduction 2 Two Important Characteristics of PTT Nanoparticles 3 Enzymatically Degradable Nanoparticles 4 Degradation by Oxidation 5 Degradation by H2O2 6 Degradation by Reduction 7 Degradation by pH 8 Laser-Inducible Degradation 9 Degradable Matrix 10 Mesoporous Silicon Nanoparticles 11 Methods to Monitor Degradation 12 Conclusions References Biohybrid Nanosystems for Cancer Treatment: Merging the Best of Two Worlds 1 Introduction 2 Biohybrids: Toolboxes and Recipes 3 Applications of Biohybrids in Cancer Therapy 3.1 Cancer Therapy 3.2 Biohybrid Nanoparticles for Cancer Therapy 3.2.1 Biohybrid Systems as Chemotherapeutic Carriers Red Blood Cells (RBCs) Cancer Cells Stem Cells Immune Cells Others 4 Applications in Cancer Immunotherapy 4.1 Cancer Immunotherapy 4.2 Biohybrid NPs for Cancer Immunotherapy 4.2.1 Activation of Antigen-Presenting Cells (APCs) 4.2.2 Combined Therapies with Immunotherapy PDT and Immunotherapy PTT and Immunotherapy Combined Immunotherapies 5 Advantages, Disadvantages, and Clinical Outlook 6 Conclusions References Electrospun Nanofibers for Cancer Therapy 1 Introduction 2 Drug-Loaded Electrospun Nanofibers for Cancer Therapy 2.1 Oil-Soluble Drug-Loaded Electrospun Fibers 2.2 Water-Soluble Drug-Loaded Electrospun Fibers 2.3 Protein-Loaded Electrospun Nanofibers 2.4 Gene-Loaded Electrospun Fibers 2.5 Other Drug-Loaded Electrospun Nanofibers 3 Functional Electrospun Nanofibers for Cancer Diagnosis 3.1 Electrospun Nanofibers for Cancer Cell Capture 3.1.1 Static Cancer Cell Capture 3.1.2 Dynamic Cancer Cell Capture 3.2 Electrospinning Sensors 3.2.1 Electrochemical Biosensor 3.2.2 Fluorescent Chemosensors 3.2.3 Gas Sensor for Lung Cancer 3.2.4 Immunosensor 4 Nanofibers for Intelligent Cancer Therapy 4.1 Nanofibers with Switchable Drug Release for Cancer Therapy 4.1.1 Magnetic-Responsive Nanofiber 4.1.2 pH-Responsive Nanofibers 4.1.3 Light-Responsive Nanofiber Ultraviolet Light-Responsive Fibers Near-Infrared Light-Responsive Fibers 4.1.4 Thermal-Responsive Nanofibers 4.2 Electrospun Nanofibers for Effective Immunotherapy of Cancer 4.3 Electrospun Nanofiber Composite for Synergistic Therapy 5 Conclusions and Future Perspectives References Nanoneedle-Based Materials for Intracellular Studies 1 Types of Nanoneedles Used for Intracellular Sensing 2 The Cell-Nanoneedle Interface 3 Delivery of Molecular Probes to Monitor Cellular Processes 4 Delivery of Probes for Multiplexed Biosensing 5 Delivery of Nanoparticles as Probes 6 Nanoneedle-Bound Optical Probes 7 Nanoneedle-Bound Probes for Cancer Biomarkers 8 Nanopipette Electrodes to Monitor Cell Metabolism 9 Multimodal Fluorescent and Electrochemical Detection of mRNA 10 Nanopipette Electrodes to Monitor Reactive Oxygen Species Generation 11 Nanoelectrodes for Metal Ion Detection 12 Nanoelectrode Arrays for Cell Sensing on the Population Scale 13 Probing Cytoskeletal Mechanics with Antibody-Conjugated AFM Tips 14 Extraction of Cellular Contents with Nanoneedle Arrays 15 Extraction of Cellular Contents: Hollow Nanostraw Arrays 16 Extraction of Cellular Contents: Single-Cell Nanobiopsy 17 Future Directions References Part III: Test, Repeat, and Test Again In Vitro Assays for Nanoparticle—Cancer Cell Interaction Studies 1 Introduction 2 2D Versus 3D Models 2.1 Multicellular Tumor Spheroid Production Techniques 2.2 MCTS Advantages 2.3 Disadvantages/Limitations 3 Multicellular Tumor Spheroids for Assessing Nanomaterials 3.1 Cellular Association/Tumor Penetration 3.1.1 Size 3.1.2 Surface Charge 3.1.3 Shape 3.1.4 Surface Modifications 3.2 Cytocompatibility and Efficacy 4 Conclusions and Future Perspectives References 3D Tumor Spheroid Models for In Vitro Therapeutic Screening of Nanoparticles 1 Introduction 2 3D Tumor Spheroid Model Versus Monolayers of Cancer Cells In Vitro 2.1 Characteristics of 3D Tumor Spheroid 2.2 3D Culture Comparison to 2D Monolayer Cultures 3 Types of Tumor Spheroids 3.1 Tumor Spheroid Cellular Heterogeneity 3.2 Multicellular Tumor Spheroids (MCTS) 3.3 Tumorospheres 3.4 Tissue-Derived Tumorospheres (TDTS) 3.5 Organotypic Multicellular Spheroids (OMS) 4 Tumor Spheroid Formation Techniques 4.1 Magnetic 3D Cell Culturing 4.2 Liquid Overlay (Forced-Floating) Method 4.3 Hanging Drop Method 4.4 Agitation-Based Methods 4.4.1 Spinner Flask Bioreactors (Spinners) 4.4.2 Rotational Culture Systems 4.5 Microfluidic Cell Culture Platforms 4.6 Scaffold-Based Culture Systems 5 Methods for Screening Nanoparticles in Spheroids 5.1 Methods for Evaluating Nanoparticle Toxicity in Spheroids 5.2 Methods for Evaluating Nanoparticle Penetration into Spheroids 5.3 Evaluation of Other Effects in Spheroids 5.4 High-Throughput Methods Developed for Spheroid Assays 6 Challenges in Testing of the Nanoparticles in 3D Tumor Spheroids 6.1 Challenges Arising from Physicochemical Properties of the Nanoparticles 6.2 Challenges Related to the Spheroid Formation and Growth 6.3 Challenges in Observing the Effect 7 Conclusions and Future Perspectives References In Vitro and In Vivo Tumor Models for the Evaluation of Anticancer Nanoparticles 1 Introduction 2 The Impact of the Tumor Microenvironment on Cancer Nanomedicine 2.1 Targeting Nanoparticles Toward the Tumor Microenvironment 2.2 The Tumors’ Intrinsic Barriers to Nanomedicine 3 Preclinical Evaluation of Anticancer Nanoparticles In Vitro 3.1 Conventional Two-Dimensional Systems 3.1.1 General Features and Limitations 3.1.2 Screening Cancer Nanoparticles in 2D Models 3.2 Emerging Three-Dimensional Tumor Models 3.2.1 Types of 3D Models and Screening Applications Multicellular Tumor Spheroids Scaffold- and Matrix-Based 3D Culture Systems Tumor Explant Cultures 3D Microfluidic Platforms Tumor-on-a-Chip Models Tumor Microenvironment-on-Chip Models 3.2.2 Third Dimension-Associated Challenges 4 In Vivo Preclinical Evaluation of Anticancer Nanoparticles 4.1 Animal Models of Cancer 4.1.1 Types of Animal Models and Screening Applications Cell Line-Derived Syngeneic/Xenograft Models Genetically Engineered Mouse Models (GEMM) Patient-Derived Xenograft Models Improving PDX Models with Avatars Humanizing PDX Models 4.2 The Challenge of Clinical Translation 5 Future Perspectives 6 Conclusions References Part IV: It Is All a Matter of Immunity Nanotechnology for the Development of Nanovaccines in Cancer Immunotherapy 1 Cancer Immunotherapy 2 Nanoparticles-Based Approaches for Cancer Immunotherapy 2.1 Micelles 2.2 Liposomes 2.3 Magnetic and Inorganic Nanoparticles 2.4 Hydrogel Nanoparticles 2.5 Polymeric Nanoparticles 2.6 Cell Membrane-Coated Nanovaccines 3 Physicochemical Characteristics Impacting Nanomedicine Application in Immunotherapy 4 Conclusions and Future Perspectives References Viral Nanoparticles: Cancer Vaccines and Immune Modulators 1 Introduction 2 Tumour Microenvironment and Oncolytic Viruses 3 Tumour Epitope Peptide-Coated Viral Nanoparticles as Cancer Vaccines 4 Cancer Membrane-Enveloped Viral Nanoparticles as Cancer Vaccines 5 Viral Nanoparticles for Delivery of Nucleic Acids 6 Current Challenges and Future Perspectives References Industrial Perspective on Immunotherapy 1 Introduction 1.1 What Is Cancer Immunotherapy? 2 How Does Cancer Immunotherapy Work? 3 The Value of Cancer Immunotherapy 4 The Current Landscape of Cancer Immunotherapy 5 Current Trends 5.1 Combination Therapy 5.2 New Indications 5.3 Identification of Predictive and Companion Biomarkers 6 Challenges 6.1 Toxicity Management 6.2 Tumour Heterogeneity and Resistance to Treatment 6.3 Clinical Development, the Path to Regulatory Approval and Beyond 6.4 Intellectual Property 7 Conclusions 8 Future Perspectives 9 The Tumour Microenvironment 10 Technical Developments 11 The Digital Revolution 12 Integration of a Patient-Centric Model References Index