Nanoparticle-Based Drug Delivery in Cancer Treatment

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Half Title
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Title Page
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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