Nanoparticle-Based Drug Delivery in Cancer Treatment

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Half Title
Series Page
Title Page
Copyright Page
Table of Contents
Preface
Author
Chapter 1 The Advantages and Versatility of Carrier-Free Nanodrug and Nanoparticle Systems for Cancer Therapy
1.1 Nanoparticles’ (NPs) Fabrication and Their Applications in Cancer Treatment
1.2 Classification of NPs
1.3 Synthesis and Characterization of NPs
1.4 Biofabrication Synthesis Methods of NPs
1.4.1 Intracellular Synthesis of NPs
1.4.2 Extracellular Synthesis of NPs
1.4.3 Cell-Free Media
1.4.4 Cell Biomass Filtrate
1.4.5 Biomolecule-Based NP Synthesis
1.4.5.1 Pigments
1.4.5.2 Proteins
1.4.5.3 Enzymes
1.4.5.4 Polysaccharides
1.5 Factors Influencing the Biofabrication of NPs Using Microorganisms
1.5.1 Illumination
1.5.2 Time of Exposure
1.5.3 pH
1.5.4 Temperature
1.5.5 Concentration of Precursors and Natural Reducing Agents
1.5.6 Nature of Microorganisms
1.6 Cyanobacteria as Biomachinery for NP Synthesis
1.6.1 Silver Nanoparticles (Ag-NPs)
1.6.2 Gold Nanoparticles
1.6.3 Colloidal Au-NPs
1.6.4 Other Nanomaterials
1.6.5 Metal Oxides and Akaganéite NPs
1.6.6 Bimetallic NPs
1.7 Passive and Active of NP Targeting Delivery in Cancer Treatment
1.8 Size and Surface Characteristics of NPs
1.9 Types of Nanocarriers Used as Controlled Delivery Vehicles for Cancer Treatment
1.10 Kinetics and Biodistribution of NPs
1.11 Mechanisms of Nanocarriers for Drug Delivery
1.11.1 Inorganic Nanocarriers
1.11.2 Organic Nanocarriers
1.11.3 Quantum Dots
1.12 Carrier-Free Nanodrugs as Anticancer Drugs
1.13 Synthetic Methods of Carrier-Free Nanodrugs
1.13.1 Direct Self-Assembly of Drug Molecules
1.13.1.1 Self-Assembly of Pure Chemotherapy Drug Molecules
1.13.1.2 Self-Assembly of Chemotherapy with PDT or PTT Drug Molecules
1.13.1.3 Self-Assembly of Chemotherapy with Immunotherapy Drugs
1.13.1.4 Self-Assembly of Chemotherapy Drugs with Other Organic Molecules
1.13.2 Self-Assembly of Clinical Drug Molecules with Different Conjugation
1.13.2.1 Conjugation of Homodimeric Drug Molecules with Various Linkers
1.13.2.2 Conjugation of Heterodimeric Drug Molecules with Various Linkers
1.13.2.3 Conjugation of Drug Molecules with Various Functional Organic Molecules
1.14 Advantages and Challenges of Carrier-Free Nanodrugs
1.14.1 Drug Loading Capacity
1.14.2 Improved Pharmacokinetic Profile and Stability
1.14.3 Enhanced Safety Profile
1.14.4 High Flexibility for Responsive Drug Release and Synergistic Combinatorial Therapy
1.14.5 Challenges
1.15 The Involvement of Drug Chemical Structure in Nanocarrier Design Development
1.16 Conclusions and Future Outlook
References
Chapter 2 Strategies, Design, and Chemistry in Small Interfering RNA Delivery Vehicle Systems for Cancer Therapy
2.1 Extracellular and Intracellular Barriers in Systemic siRNA Delivery to Solid Tumors
2.2 Design Criteria to Overcome Extracellular Barriers
2.3 Design Criteria to Overcome Intracellular Barriers
2.4 Design of siRNA Delivery Vehicles
2.5 Carrier Design for Stability and Release
2.5.1 Hydrophobicity-stabilized Delivery Vehicles
2.5.2 Delivery Carrier Design for Selective Release of siRNA
2.5.2.1 Redox Potential Responsive Delivery Vehicles
2.5.2.2 Acidic pH Responsive Delivery Vehicles
2.5.2.3 ATP Concentration-responsive Delivery Vehicles
2.6 Delivery Carrier Design for High Cell Specific Recognition
2.6.1 Biological Stimuli-responsive Delivery Vehicles
2.6.2 Ligand Installed Delivery Vehicles
2.7 Delivery Vehicles for High Endosomal Escapability
2.8 Delivery Carrier Design in Other Category
2.8.1 Layer-by-layer Delivery Vehicle
2.8.2 Calcium Phosphate-formulated Delivery Vehicles
2.8.3 Gold Nanoparticle-templated Delivery Vehicles
2.9 Synthesis of siRNA and Chemical Modification of Nucleotides
2.9.1 Nucleotides Modification
2.9.2 Synthesis of siRNA
2.10 siRNA-ligand Conjugates
2.11 Nucleotides Derived Nanoparticles
2.12 Lipid-based Delivery Systems
2.12.1 Lipid Analogs with Cationic Head Groups and Hydrophobic Tails
2.13 Conclusions
References
Chapter 3 DNA/RNA Nanoparticles Structures for siRNA Delivery Applications
3.1 Structural DNA-/RNA-based RNAi Systems
3.2 Poly/Multimeric siRNA Delivery Applications
3.2.1 Long Linear siRNA
3.2.2 Branched siRNA
3.2.3 Novel Carriers for Poly/Multimeric siRNA Delivery
3.3 Three-dimensional RNA/DNA Structures for siRNA Delivery Applications
3.3.1 RNA-based Nanoparticles for siRNA Delivery
3.3.2 DNA Polyhedron Nanoparticles for siRNA Delivery
3.3.3 Large-scale Preparation of DNA Nanostructures for Translational Study
3.4 DNA/RNA Ball Technology for siRNA Delivery Applications
3.4.1 RNA Microsponge/Ball Technology for siRNA Delivery
3.4.2 Microscopic DNA Scaffolds for Gene Delivery
3.5 DNA/RNA Nanoparticles
3.5.1 pRNA Nanoparticles
3.5.2 RNA Nanoring
3.5.3 Tetrahedron Oligonucleotide Nanoparticles
3.6 Conclusions
References
Chapter 4 Codelivery in Nanoparticle-based siRNA for Cancer Therapy
4.1 Nanocarriers to Deliver RNA (siRNA) Chains
4.2 Mechanisms of Cancer Drug Resistance
4.3 Alterations in the Membrane Transporters or Efflux Pumps
4.4 Activation of Antiapoptotic Pathways
4.5 Sensitization Strategies for siRNA-based Therapeutics
4.6 Efflux Pump–related Sensitization Strategies
4.7 Nonefflux Pump–related Sensitization Strategies
4.8 Nanocarriers to Codeliver siRNA and Small Drugs
4.9 Polymeric Nanoparticles
4.9.1 Cyclodextrin Nanoparticle
4.9.2 Chitosan Nanoparticles
4.9.3 Polyethyleneimine
4.9.4 PLGA
4.9.5 Dendrimers
4.10 Inorganic Nanoparticles
4.11 Inorganic-based Nanoparticles
4.12 Polymer-based Nanoparticles
4.13 Lipid-based Nanoparticles
4.14 Lipid-based Delivery
4.15 Bioconjugated siRNAs
4.16 Targeted Delivery
4.17 Clinical Trials
4.18 Conclusions
References
Chapter 5 Small Interfering RNAs, MicroRNAs, and NPs in Gynecological Cancers
5.1 Introduction
5.2 siRNA Technology in Cancer Therapy
5.3 siRNA-Based Gene Silencing
5.4 Off-Target Effects and Stimulation of Immune Response
5.5 Delivery Systems
5.5.1 Lipid-Based Nanovectors for siRNA Delivery
5.5.2 Liposomes and Lipoplexes
5.5.3 Stable Nucleic Acid Lipid Particles (SNALPs)
5.6 Polymeric Nanoparticles
5.6.1 Cyclodextrin (CD) Nanoparticles
5.6.2 Chitosan and Inulin Nanoparticles
5.6.3 Polyethylenimine (PEI)
5.6.4 Anionic Polymers
5.6.5 Cationic Dendrimers
5.7 Carbon Nanotubes (CNTs)
5.8 Inorganic Nanoparticles (INPs)
5.8.1 Magnetic Nanoparticles (MNPs)
5.8.2 Gold Nanoparticles (AuNPs)
5.9 Limitations to the siRNA Therapeutic Approach
5.10 siRNA in Clinical Trials for Cancer Therapy
5.11 Gynecological Cancers (GCs)
5.12 Dysregulation of miRNAs in Gynecological Cancers
5.12.1 Ovarian Cancer
5.12.2 Cervical Cancer
5.12.3 Endometrial Cancer
5.13 Biological Significance of miRNAs in Gynecological Cancers
5.13.1 Cell Proliferation, Survival, and Stemness
5.13.2 Invasion and Metastasis
5.13.3 Modulation of Tumor Microenvironment
5.13.4 Chemoresistance Mechanisms
5.14 Clinical Significance of miRNAs in Gynecological Cancers
5.14.1 Tools for Early and Differential Diagnosis
5.14.2 Predictive and Prognostic Biomarkers
5.14.3 Next-Generation of Therapeutics
5.15 Conclusion and Future Perspectives
References
Chapter 6 Nanoparticle–Based RNA (siRNA) Combination Therapy Toward Overcoming Drug Resistance in Cancer
6.1 Small Interference RNA (siRNA)
6.2 Novel Combination Therapy
6.3 Nanoparticulate Systems for Combinatorial Drug Delivery
6.3.1 Liposomes
6.3.2 Polymeric Nanoparticles
6.3.3 Polymer–Drug Conjugates
6.3.4 Dendrimers
6.3.5 Other Nanoparticles
6.4 Lipid-Based Nanovectors for Systemic siRNA Delivery
6.4.1 Liposomes/Lipoplexes
6.4.2 Stable Nucleic Acid Lipid Particles and Lipidoids
6.5 Combinatorial Nanoparticles against Multidrug Resistance in Cancer
6.5.1 Combination of Efflux Pump Inhibitors with Chemotherapeutics
6.5.2 Combinations of Pro-apoptotic Compounds with Chemotherapeutics
6.5.3 Combinations of MDR-Targeted siRNA with Chemotherapeutics
6.6 Combination Strategies against Clinical Cancer Drug Resistance
6.6.1 Combinatorial Nanoparticles Co-encapsulating Hydrophobic and Hydrophilic Drugs
6.6.2 Combinatorial Nanoparticles with Precise Ratiometric Drug Loading
6.6.3 Combinatorial Nanoparticles with Temporally Sequenced Drug Release
6.7 Gold Nanoparticles Radiosensitization Effect in Radiation Therapy of Cancer
6.8 Interaction of X-Ray and Gamma Radiations with GNPs
6.9 Monte Carlo Modeling of GNP Dose Enhancement Effect
6.10 GNP Sensitization in Cell Line and Animal Models
6.11 Impact of Radiation Energy
6.12 Biomedical Applications of Graphene Oxide (GO)
6.12.1 Characterization of GOs
6.12.2 Induction of Apoptosis by GOs in Endothelial Cells (ECs)
6.12.3 Inhibition of Autophagy Attenuates SGO- or NGO-Induced Apoptotic Cell Death
6.12.4 SGO or NGO Increases Intracellular Ca[sup(2+)] Levels by Activating Calcium Channels, and Elevated Intracellular Ca[sup(2+)] Activate Subsequent Downstream Intracellular Events Related to GO-Mediated Autophagy
6.13 Conclusion and Outlook
References
Chapter 7 Advantages and Limitations of RNAi Delivery for Cancer Biological Therapeutics Imaging
7.1 Introduction
7.2 RNAi Cancer Therapeutics in Clinical Trials
7.3 Biological Barriers for RNAi Cancer Therapeutics
7.3.1 Administration Barrier
7.3.2 Vascular Barrier
7.3.3 Cellular Barrier
7.3.4 Immune Response and Safety
7.4 Imaging Modalities in the RNAi Cancer Therapeutics Development Process
7.4.1 Optical Imaging
7.4.2 PET and SPECT
7.4.3 MRI
7.4.4 Ultrasound
7.4.5 Multimodality Imaging
7.5 Theranostic Nanomedicines
7.6 Preparation of Nanogels and Triggered Drug Release
7.7 Cellular Uptake and Cytotoxicity of PTX-Loaded HAI-NGs
7.8 In Vivo Pharmacokinetics, Near Infrared Imaging, and Biodistribution of Nanogels
7.9 Enhanced CT Imaging by HAI-NGs
7.10 In Vivo Tumor Penetration and Therapeutic Efficacy of PTX-Loaded HAINGs
7.11 Conclusions and Perspectives
References
Chapter 8 Recent Development of Silica Nanoparticles as Delivery Biomedical Applications for Cancer Imaging and Therapy
8.1 Nanotechnology in Cancer Diagnosis and Therapy
8.2 Characteristics of Silica Nanoparticles
8.2.1 Particle Size
8.2.2 Surface Modification
8.3 Imaging Applications of Silica Nanoparticles
8.3.1 Fluorescence Imaging
8.3.2 Magnetic Resonance Imaging (MRI)
8.4 Drug and Gene Delivery Using Silica Nanoparticles
8.4.1 Drug Delivery
8.4.2 Chemotherapeutic Agents
8.4.3 Photodynamic Therapy Agents
8.4.4 Gene Therapy Using SiNPs-Based Vectors
8.5 Multifunctional Silica Nanoparticles
8.6 Biocompatibility of Silica Nanoparticles
8.7 Mesoporous Silica Nanoparticles (MSNPs)
8.8 Preparation and Properties of the Functional Molecules Coated MSNs
8.8.1 MSNs
8.8.2 Lipid-Coated MSNs
8.8.3 Protein-Coated MSNs
8.8.4 Poly(NIPAM)-Coated MSNs
8.9 Potential Applications and Outlooks
8.9.1 In Photodynamic Therapy
8.9.2 In Cell Imaging
8.9.3 In Controlled Release
8.9.4 In Selective Recognition
8.10 Conclusions
References
Chapter 9 Application of Carbon Nanotubes in Cancer Vaccines as Drug Delivery Tools
9.1 Introduction
9.2 Carbon Nanotubes
9.3 Carbon Nanotubes (CNTs) As Nanocarriers
9.3.1 Spheres Vs Tubes Vs Sheets As Nanocarriers
9.3.2 Mechanisms of CNTs’ Cellular Uptake
9.3.3 CNTs’ Biocompatibility In Vitro
9.3.3.1 Effect of CNTs’ Chemical Functionalization
9.3.3.2 Biocompatibility with Immune Cells
9.4 CNT Functionalization Techniques
9.4.1 Noncovalent Functionalization
9.4.2 Covalent Functionalization
9.5 CNTs’ Biodistribution
9.6 Functionalized CNTs As Cancer Vaccine Delivery System
9 6.1 Functionalized CNTs As Delivery Vector for Tumor-Derived Antigen
9.6.2 Functionalized CNTs As Delivery Vector for Adjuvants
9.6.3 Functionalized CNTs As Delivery Vector for Both Tumor-Derived Antigen and  Adjuvants
9.7 CNTs in Drug Delivery
9.7.1 Covalent Drug Attachment to CNTs
9.7.2 Noncovalent Drug Attachment to CNTs
9.8 Delivery of Chemotherapeutics
9.8.1 CNT–Doxorubicin Complexes
9.8.2 CNT–Methotrexate Constructs
9.8.3 CNT–Taxane Constructs
9.8.4 CNT–Platinum Constructs
9.8.5 CNT–Camptothecin Constructs
9.8.6 CNT–Gemcitabine Constructs
9.9 Delivery of Immunotherapeutic
9.10 Delivery of Nucleic Acids
9.11 Loading CNTs with Anticancer Drugs
9.12 Cellular Targeting and Uptake of CNTs
9.13 Drug Release from CNTs
9.14 CNTs in Thermal Ablation of Cancer Cells
9.15 Alternative Anticancer Strategies: Thermal Ablation and Radiotherapy
9.16 Tumor-Targeted CNT
9.17 CNTs in Gene Therapy
9.18 Toxicity of CNT
9.19 Future Perspective of CNTs As Vaccine Delivery Systems
9.20 Conclusion and Future Directions
References
Chapter 10 Development of Oligonucleotide Delivery, (siRNAs), and (miRNA) Systems for Anticancer Therapeutic Strategy Immunotherapy
10.1 Drug Delivery Systems
10.2 Short-Interference RNA as a Potential Treatment of Liver Diseases
10.2.1 Current Reports Regarding Delivery of siRNA to Liver Tissue
10.2.2 YSK-MEND, Lipid Nanoparticles for the Delivery of siRNA to the Liver
10.2.3 Challenge to Treating HBV Infections Using the YSK-MEND
10.3 MEND System Meets to Cancer Immunotherapy
10.3.1 STING Ligand, Cyclic di-GMP, Loaded Nanoparticles for Cancer Immunotherapy
10.3.2 Enhancement of Dendritic Cell –Based Immunotherapy against Cancer by siRNA- Mediated Gene Silencing
10.3.3 Lipid Antigen Delivery: New Strategy for Immunotherapy
10.4 Mitochondria, a Candidate for a Target Organelle in Cancer Therapy
10.4.1 Current State of Our Knowledge Regarding Mitochondrial DDS Focusing on Cancer Therapy
10.4.2 MITO-Porter: A Liposome for Mitochondrial Delivery
10.4.3 Challenge to Cancer Therapy by the Mitochondrial Delivery of Therapeutics Using a MITO-Porter
10.5 Immunomodulation of Hematological Malignancies
10.6 The Requirements from Oligonucleotide Delivery Systems for Site-Specific Targeting to
Malignant Leukocytes
10.7 Systemic Delivery of Inhibitory Oligonucleotides to Malignant Leukocytes
10.7.1 ASOs and siRNA-CpG
10.7.2 Aptamers
10.8 Supramolecular NCs for Systemic Delivery of Inhibitory Oligonucleotides into Blood Cancers
10.8.1 Polymer-Based Delivery Systems
10.8.2 Lipid-Based Delivery Systems
10.8.2.1 Liposomes
10.8.2.2 Stabilized Nucleic Acid Lipid Particles
10.9 Future Outlook
References
Chapter 11 Pharmacogenomics Synergistic Strategies Using a Chimerical Peptide for Enhanced Chemotherapy Based on ROS and DNA Nanosystem
11.1 Chemotherapy As Synergistic Gene
11.2 Characterization of Peptide and Complexes
11.3 Drug Loading and Release Behavior In Vitro
11.4 Endosome Escape Capability
11.5 Gene Transfection In Vitro
11.6 In Vitro Cytotoxicity
11.7 Codelivery of Drug and Gene In Vitro
11.8 Synergistic Effect In Vitro
11.9 Antitumor Effect In Vivo
11.10 ROS-Triggered Self-Accelerating Drug Release Nanosystem
11.11 Characterization of T/D@RSMSNs
11.12 Evaluation of ROS-Responsive Drug Release
11.13 Analysis of the ROS-Regenerating Ability of ?-TOS In Vitro
11.14 Intracellular ROS-Triggered Amplifying ROS Signals and Self-Accelerating Drug Release
11.15 Evaluation of Cytotoxicity In Vitro of MSN
11.16 Antitumor experiments In Vivo Via Intravenous Injection
11.17 Platinum-Based Combination Chemotherapeutic Drugs
11.17.1 Cell and RNA Preparation
11.17.2 Classification of Platinum Response in Ovarian Tumors
11.17.3 Cross-Platform Affymetrix GeneChip Comparison
11.17.4 Cell Proliferation and Drug Sensitivity Assays
11.18 Developing a Gene Expression–Based Predictor of Cisplatin Sensitivity
11.18.1 Developing a Gene Expression–Based Predictor of Pemetrexed Sensitivity
11.19 In Vitro Validation of the Cisplatin and Pemetrexed Predictor
11.19.1 In Vivo Validation of the Cisplatin Sensitivity Predictor
11.20 Patterns of Predicted Chemotherapy Response to Cisplatin and Pemetrexed in NSCLC
11.21 The Sequence of Chemotherapy May Be Critical in Optimizing Responses
11.22 Conclusions
References
Chapter 12 Pharmacokinetics, Biodistribution, and Therapeutic Applications of Recently Developed siRNA and DNA Repair Genes Recurrence
12.1 RNAi as a Potential Therapeutic
12.2 Therapeutic Applications of siRNA and Target Genes
12.2.1 Ocular Diseases
12.2.2 Cancer
12.2.3 Liver Diseases
12.2.3.1 HCC
12.2.3.2 Hepatic Viral Infections (Table 12.3)
12.2.4 Respiratory Diseases
12.3 Pharmacokinetics of siRNA Therapeutics
12.3.1 Preclinical Studies
12.3.2 Clinical Studies
12.4 Biodistribution of siRNA Therapeutics
12.4.1 Tracking siRNA Labeled with Fluorescent Dyes
12.4.2 Tracking Radiolabeled siRNA
12.4.3 Tracking siRNA Itself
12.4.4 Tracking Carriers
12.4.5 Targeted vs. Non-Targeted
12.5 Pharmacological Effects of siRNA Therapeutics
12.5.1 Liver Diseases
12.5.1.1 HCC
12.5.1.2 Liver Infections
12.5.2 Respiratory Diseases
12.5.3 Potential Toxicity of siRNA Therapeutics
12.6 DNA Recurrence-associated Genes
12.6.1 Functional Enrichment Analyses
12.7 Genomic Global Analysis of the TCGA
12.8 Conclusions
References
Chapter 13 Nanotechnologies Assemblies of siRNA and Chemotherapeutic Drugs Codelivered for Cancer Therapeutic Applications
13.1 Double-stranded RNA (dsRNA)
13.2 siRNA Mechanism
13.3 siRNA Delivery Challenges
13.3.1 General Delivery Barriers
13.3.2 Local Delivery Considerations
13.4 siRNA Modifications and Carriers
13.5 Local Delivery Strategies
13.5.1 Microparticles
13.5.2 Scaffolds
13.5.3 Electrospun Fibers
13.5.4 Hydrogels
13.5.5 Surface Coatings
13.6 Therapeutic Applications
13.6.1 Tissue Regeneration
13.6.2 Directing Cellular Differentiation
13.6.3 Bone Pathologies
13.6.4 Angiogenesis and Wound Healing
13.6.5 Fibrosis
13.6.6 Inflammation
13.6.7 Microbial Infections
13.6.8 Clinical Prospects
13.6.9 Cancer
13.7 siRNA for Colorectal Cancer Therapy
13.8 Nanoassemblies for Combinatorial Delivery of siRNA
13.8.1 Synthesis and Characterization of Block Copolymers
13.8.2 Study on Cell Uptake
13.9 Liposomes and siRNA Delivery for Melanoma Therapy
13.9.1 Intracellular Localization of the Lipoplexes and Protein Expression Knockdown
13.10 Targeted Delivery: Mechanistic Pathway
13.11 Magnetic Field for Cancer Treatment
13.12 Electric Field for Cancer Therapy
13.13 Thermal Treatment for Cancer Therapy
13.14 Differential Drug Delivery to Tissues, a Goal of DDS
13.15 Future Challenges in Cancer Therapy
References
Chapter 14 Targeted Systemic Combinatorial Delivery of siRNA Polyplexes–Functional Quantum Dot-siRNA Nanoplexes
14.1 Targeted Systemic Delivery of siRNA to Cervical Cancer Model
14.1.1 Preparation and Physicochemical Characterizations of Targeted uPIC-AuNP
14.1.2 In Vitro siRNA Delivery by Targeted uPIC-AuNP
14.1.3 In Vivo Tumor Accumulation and Gene Silencing of cRGD-uPIC-AuNP
14.1.4 In Vivo Tumor Growth Inhibition by Intravenous Administration of siE6-Loaded cRGD-uPIC-AuNP
14.2 Targeted Combinatorial siRNA Polyplexes
14.3 Oligomer Synthesis and Formation of Targeted Combinatorial Polyplexes (TCPs)
14.4 Functional Quantum Dot-siRNA Nanoplexes
14.4.1 Characterization of QD-SMCC-siRNA
14.4.2 Cellular Ultrastructural Response to the QD-SMCC-siRNAs
14.4.3 Quantification of the Transfection Efficiency of QD-SMCC-si In Vitro
14.4.4 In Vivo Fluorescence Imaging and Histological Evaluation
14.4.5 Silencing Efficiency of QD-SMCC-si and Suppression of SOX9 In Vivo
14.5 Conclusions
References
Chapter 15 Recent Advances of Nanotechnologies for Cancer Immunotherapy Treatment
15.1 Basics of Immunotherapy and the Tumor Microenvironment
15.1.1 Nanotechnology in Cancer Immunotherapy
15.2 Delivery of Tumor Vaccines by Nanoparticles for Tumor Immunotherapy
15.3 Antigenic Peptide-Based Nanovaccines
15.3.1 Polymeric Nanocarriers
15.3.1.1 PLGA Nanoparticles
15.3.1.2 Micellar Nanocarriers
15.3.1.3 Hydrogel Nanoparticles
15.3.2 Liposomes
15.3.3 Exosomes
15.3.4 Gold Nanoparticles
15.3.5 Mesoporous Silica Nanoparticles (MSNs)
15.3.6 Carbon Nanotubes (CNTs)
15.4 Nanoparticles Delivering Immune Checkpoint Inhibitors
15.5 The Basic Mechanism of Cytotoxic T Lymphocyte Antigen-4 (CTLA-4)
15.5.1 Antibodies Blocking CTLA-4
15.5.2 Combination Therapies Based on CTLA-4 Blockade
15.5.2.1 Synergistic Effects by Combining Drug-Loaded Nanoparticles with Immune Checkpoint Inhibitors
15.5.3 siRNA Targeting CTLA-4 Immune Checkpoint
15.6 The Basic Mechanism of PD-1/PD-L1 Axis
15.6.1 Antibodies Blocking PD-1/PD-L1 Pathway
15.6.2 Combination Therapies Based on PD-1/PD-L1 Pathway Blockade
15.6.2.1 Enhanced Antitumor Effect by Combination of Therapeutic Agents and Immune Checkpoint Inhibitors
15.6.2.2 Synergistic Effects by Combining Drug-Loaded Nanoparticles with Immune Checkpoint Inhibitors
15.6.2.3 Combination Therapy with Immune Checkpoint Inhibitors Loaded Nanoparticles
15.6.3 siRNA Targeting PD-1/PD-L1 Immune Checkpoint
15.7 The Basic Mechanism of IDO
15.7.1 Inhibitors Blocking IDO
15.7.2 Combination Therapies Based on IDO Blockade
15.7.3 siRNA Targeting IDO Immune Checkpoint
15.8 C D47, CD40, and 4-1BB
15.9 Opportunities for Improving Efficacy of Immune Checkpoint Inhibitors
15.10 Prospects for Immune Checkpoint Blockade
15.11 Targeted Delivery of Nanoparticles to Lymph Nodes and Immune Cells
15.12 Nanoparticles Influencing the Tumor Microenvironment for Immunotherapy Enhancement.
15.13 Nanoparticles in Enhancing Adoptive Cell Therapy
15.14 Nucleic Acid-Based Nanovaccines
15.14.1 Polymeric Nanoparticles
15.14.1.1 siRNA Polymeric Nanoparticles
15.14.1.2 Oligodeoxynucleotide (ODN) Polymeric Nanoparticles
15.14.1.3 pDNA Polymeric Nanoparticles
15.14.2 Lipid-Based Nanoparticles (LNPs)
15.14.2.1 siRNA LNPs
15.14.2.2 Oligonucleotides LNPs
15.14.2.3 pDNA LNPs
15.14.2.4 mRNA LNPs
15.15 Monoclonal Antibody (mAb)
15.16 Small Molecule Nanomedicines
15.17 Conclusion, Challenges, and Perspective
15.18 Future Directions
References
List of Abbreviations
Index