Nano Drug Delivery for Cancer Therapy: Principles and Practices

Preface
About the Book
Contents
Editor and Contributors
1: Significance of Nano-drug Delivery in Cancer Therapy, Application of Nanoparticles in Overcoming Drug Resistance, Targeted ...
	1.1 Introduction
	1.2 Overview History of Nanotechnology and Nanoparticles
	1.3 Significance of Nano-Based Carriers Carrying Anticancer Agents
	1.4 Various Types of Nanoparticles Are Used in Drug Delivery Systems
	1.5 Organic Nanoparticles
		1.5.1 Liposomes
		1.5.2 Dendrimers
		1.5.3 Carbon Nanoparticles and Nanotubes
		1.5.4 Polymeric Nanocarriers
		1.5.5 Polymeric Micelles
		1.5.6 Polymeric Nanoparticles
		1.5.7 Inorganic Nanoparticles
		1.5.8 Gold NPs
		1.5.9 Iron Oxide NPs
		1.5.10 Silica NPs
		1.5.11 Magnetic Nanoparticles
		1.5.12 Quantum Dots
		1.5.13 Hybrid Nanoparticles
	1.6 Application of Nanocarriers in Drug Resistance to Cancer
		1.6.1 Application of Nanoparticles in Overcoming Drug Resistance
		1.6.2 Application of Nanoparticles in Targeted Therapy
		1.6.3 Application of Nanoparticles in Immunology
		1.6.4 Mechanisms of Nanocarriers in Overcoming Drug Resistance Problems
			1.6.4.1 Enhanced Permeability and Retention (EPR) Effect
			1.6.4.2 Passive and Active Targeting
			1.6.4.3 Multidrug Resistance (MDR) Modulation
			1.6.4.4 Co-delivery of Multiple Drugs
			1.6.4.5 Controlled Drug Release
	1.7 The Role of Nanoparticles in Immunotherapy
		1.7.1 Nanoparticles as the Carrier of Immunotherapeutic Agents
		1.7.2 Antigens and Adjuvants Delivery to Antigen-Presenting Cells (APCs)
		1.7.3 Antigens and Adjuvants Delivery to Tumor Microenvironment (TME)
		1.7.4 Nanoparticles as the Direct Immunomodulators
		1.7.5 Targeting Dendritic Cells
	1.8 Conclusion and Future Perspectives
	References
2: Synthesis of Different Types, Shapes, and Sizes of Nanocarriers Using Synthetic and Biological Approaches
	2.1 Nanomaterials Synthesis Methods
		2.1.1 0D Nanomaterials
			2.1.1.1 Metal NPs
				2.1.1.1.1 Co-precipitation Method
				2.1.1.1.2 Polyol Method
				2.1.1.1.3 Green Synthesis
			2.1.1.2 Metal Oxide NPs
				2.1.1.2.1 Sol-Gel Method
				2.1.1.2.2 Solvothermal/Hydrothermal Method
				2.1.1.2.3 Co-precipitation Method
				2.1.1.2.4 Combustion Method
				2.1.1.2.5 Sonochemical Synthesis
				2.1.1.2.6 Green Synthesis
			2.1.1.3 Polymeric NPs
				2.1.1.3.1 Microemulsion Method
		2.1.2 1D Nanomaterials
			2.1.2.1 Template Synthesis Method
		2.1.3 2D Nanomaterials
		2.1.4 3D Nanomaterials
	References
3: Synthesis of Nanocarriers Loaded with Anti-Cancer Drugs by Using Functionalization or Conjugations, Encapsulation Methods
	3.1 Introduction
		3.1.1 Functionalized Graphene Oxide
			3.1.1.1 Conjugation and Functionalization of Graphene Oxide Based Nanocarriers
	References
4: Nano-Drug Carriers for Chemotherapeutic Agents Delivery in Cancer Disease Treatment
	4.1 Introduction
	4.2 Lipid-Based Nanotherapy
		4.2.1 Solid Lipid Nanoparticles
		4.2.2 Liposomes
		4.2.3 Lipid Emulsions
	4.3 Carbon-Based Nanotherapy
		4.3.1 Carbon Nanotubes/Carbon Nanofibers
		4.3.2 Carbon Dots
	4.4 Dendrimers Based Nanotherapy
	4.5 Protein-Based Nanotherapy
	4.6 Synthetic Polymer-Based Nanotherapy
		4.6.1 PLGA Nanoparticles
		4.6.2 PLA and PBCA Nanoparticles
	4.7 Metal-Based Nanotherapy
		4.7.1 Mesoporous Silica Nanoparticles (MSNs)
		4.7.2 Iron Oxide Nanoparticles
		4.7.3 Zinc Oxide Nanoparticles
		4.7.4 Inert Metals Nanoparticles
	4.8 Combinatorial Nanoparticles
	4.9 Conclusion
	4.10 Future Perspectives
	References
5: Testing of Nanocarriers Loaded with Chemotherapeutic Agents in the Animal Models of Cancers: Preclinical Trials for Efficac...
	5.1 Cancer
		5.1.1 Historical Turning Points in Cancer
		5.1.2 Treatment of Cancer
		5.1.3 Introduction to Nanotechnology
	5.2 Applications of Nanotechnology
		5.2.1 Nanomaterials Used for Cancer Therapy
			5.2.1.1 Polymeric Nanoparticles
			5.2.1.2 Lipid-Based Nanomaterials
			5.2.1.3 Nanoemulsions
			5.2.1.4 Carbon Nanoparticles
		5.2.2 Use of Nanocarriers in Cancer Therapy
		5.2.3 Opportunities and Challenges of Nanoparticles for Cancer Therapy
	5.3 Preclinial Testing of Nanocarriers
		5.3.1 Uses of Animal Model
		5.3.2 Various Animal Models Employed in Cancer Models
			5.3.2.1 Canine Cancer Models
			5.3.2.2 Patient-Derived Xenograft (PDX) Model
			5.3.2.3 Mouse Models
			5.3.2.4 Transgenic Mouse Models (of Breast Cancer): The MMTV Paradigm
			5.3.2.5 Zebrafish Model
	5.4 Hu-PBL Model
	5.5 Toxicities of Nanocarriers
	5.6 Safety Profiling of Nanoparticles
		5.6.1 Importance of Safety Profiling
		5.6.2 Current Methods of Safety Profiling
		5.6.3 Challenges and Limitations
		5.6.4 Future Directions
	References
6: Testing of Nanocarriers Loaded with Chemotherapeutic Agents: Cancer Patients and Clinical Trials
	6.1 Clinical Trials and Different Phases
	6.2 Application of Nanocarriers in Anticancer Drug Delivery
		6.2.1 Poly (Lactic-Co-Glycolic Acid) (PLGA) Nanocarriers
		6.2.2 Magnetic Nanoparticle-Based Nanocarriers
		6.2.3 Plant-Based Nanocarriers
	6.3 Clinical Trials of Nano-Based Formulation for Cancer Diagnosis and Therapy-Completed Trials
	6.4 FDA Approved Nano-Based Materials for Cancer
		6.4.1 Polymer Nanoparticles-Synthetic Polymer Particles Combined with Drugs or Biologics
		6.4.2 Liposome Formulations Combined with Drugs or Biologics
		6.4.3 Micellar Nanoparticles Combined with Drugs or Biologics
		6.4.4 Nanocrystals
	6.5 Conclusion
	References
7: Nanocarriers-Based Products in the Market, FDA Approval, Commercialization of Nanocarriers, and Global Market
	7.1 Commercialization of Nanomedicine Products
	7.2 Process of Commercialization Nanomedicine Products
		7.2.1 Identification of Problem
		7.2.2 Finding Solution
		7.2.3 Research and Invention
		7.2.4 Disclosure of Invention
		7.2.5 Assessment of Invention
		7.2.6 Issuing of Patent
		7.2.7 Licensing of Patented Technology
		7.2.8 Preclinical and Clinical Trials
		7.2.9 Approval of the Product
		7.2.10 Marketing of Product
	7.3 Nanomaterials as Commercial Products
	7.4 Global Market of Nanomedicine Products
		7.4.1 Market Classification of Nanomedicine Products
		7.4.2 Leading Players in Nanomedicine Market
	7.5 Nanomedicine for Cancer Therapy
	References
8: Limitations of Nanocarriers Such as Cell and Tissue Toxicity, Genotoxicity, Scale-Up of Nanomaterials
	8.1 Introduction
	8.2 Nanomaterials and Their Biomedical Applications
	8.3 Limitations Faced by Drug Loaded Nanocarriers
		8.3.1 Immune System (IS) and Nanocarriers
			8.3.1.1 Innate Immune System
			8.3.1.2 Adaptive Immune System
		8.3.2 Blood-Brain Barrier (BBB)
	8.4 Toxicity of Nanocarriers
		8.4.1 Cellular Toxicity of Nanocarriers
		8.4.2 Gene Toxicity
		8.4.3 Accumulation in Organs
	8.5 Scale-Up of Nanocarriers
	8.6 Conclusion
	References
9: Health and Environmental Hazards Associated with the Synthesis of Nanomaterials-Respiratory Diseases, Government Regulation...
	9.1 Introduction
	9.2 Types of Nanoparticles
	9.3 Harmful Effects of Nanomaterials
	9.4 Impact of Nanomaterials-Induced Toxicity
	9.5 Methods of Evaluating Nanomaterial-Induced Toxicities
		9.5.1 In Vitro Method of Testing
		9.5.2 In Vivo Method of Testing
	9.6 Reduction of Nanoparticles Toxicity
	9.7 Nanomaterials and Regulations for Preventing Health Hazards
	References
10: Future Trends and Innovation in Nano Drug Delivery for Cancer Therapy, Application of siRNA (Nanoparticle-Based RNA) Thera...
	10.1 Introduction
	10.2 NPs in Cancer Therapy
	10.3 NPs Used for Drug Delivery in Cancer Therapy
		10.3.1 Inorganic NPs for Drug Delivery in Cancer Therapy
			10.3.1.1 Liposomes
			10.3.1.2 Polymeric Nanoparticles
			10.3.1.3 Peptides and Protein Nanoparticles
		10.3.2 Micelles NPs
		10.3.3 Self-Assembled Drug NPs
	10.4 Targeted Drug Delivery
		10.4.1 Passive Targeting
			10.4.1.1 Limitations in Passive Targeting
		10.4.2 Active Targeting
		10.4.3 Targeting to Cancer Cells
			10.4.3.1 Epidermal Growth Factor Receptor (EGFRs)-Based Active Targeting
			10.4.3.2 Transferrin (Tf) Receptor-Mediated Active Targeting
			10.4.3.3 Estrogen Receptor-Mediated Active Targeting
			10.4.3.4 Cluster of Differentiation (CD) Receptor-Mediated
			10.4.3.5 Folate Receptor (FR)-Mediated Active Targeting
			10.4.3.6 Glycoproteins-Mediated Active Targeting Systems
			10.4.3.7 Other Receptor-Mediated Active Targeting Systems
		10.4.4 Targeting to Endothelium
	10.5 Stimuli-Responsive Targeting Strategies
		10.5.1 Endogenous Stimuli
			10.5.1.1 pH-Responsive Targeting Strategies
			10.5.1.2 Redox-Responsive Targeting Strategies
			10.5.1.3 Enzyme-Responsive Targeting Strategies
			10.5.1.4 Hypoxia-Responsive Targeting Strategies
			10.5.1.5 ATP-Responsive Targeting Strategies
			10.5.1.6 Tumor-Metabolite Responsive Targeting Strategies
		10.5.2 Exogenous Stimuli
			10.5.2.1 Temperature Stimuli-Responsive Targeting Strategies
			10.5.2.2 Magnetic Stimuli-Responsive Targeting Strategies
			10.5.2.3 Light Stimuli-Responsive Targeting Strategies
			10.5.2.4 Ultrasound Stimuli-Responsive Targeting Strategies
	10.6 Stimuli-Responsive Gene Delivery Nanocarriers for Cancer Therapy
	10.7 Application of siRNA (Nanoparticle-Based RNA) Cancer Therapy
		10.7.1 Introduction
		10.7.2 Difficulties in siRNA Delivery
			10.7.2.1 Physiological Barriers
			10.7.2.2 Cell Membrane
			10.7.2.3 Stability
			10.7.2.4 Off-Target Effects
		10.7.3 Applications of Nanocarriers for siRNA Delivery
		10.7.4 Nanocarriers for Co-delivery of siRNA with Anticancer Drug
		10.7.5 Clinical Applications of siRNA-Based Nanotherapies
		10.7.6 Current Challenges and Opportunities
		10.7.7 Design Concerns for Future Development of RNAi-Mediated Anticancer Nanotherapeutics
	10.8 Ultrasound Linked Nano-cancer Therapeutics
		10.8.1 Introduction
		10.8.2 Ultrasound Parameters Used for Cancer Therapy
		10.8.3 Ultrasound Interactions with Nanoparticles
		10.8.4 Types of Ultrasound-Sensitive Materials and Nanoparticles
	10.9 Exosomes as Anticancer Drug Delivery Vehicles
		10.9.1 Introduction
		10.9.2 Biogenesis and Uptake of Exosomes
		10.9.3 The Sources of Exosomes
		10.9.4 Isolation of Exosomes
			10.9.4.1 Ultracentrifugation
			10.9.4.2 Ultrafiltration
			10.9.4.3 Size Exclusion Chromatography (SEC)
			10.9.4.4 Flow Field-Flow Fractionation (F4)
			10.9.4.5 Hydrostatic Filtration Dialysis (HFD)
			10.9.4.6 Polymer-Based Precipitation
			10.9.4.7 Immunoaffinity Capture-Based Technology
			10.9.4.8 Microfluidic-Based Exosome Isolation
		10.9.5 Drug Loading on Exosomes
			10.9.5.1 Presecretory Drug Loading
				10.9.5.1.1 Co-Incubation (Drug and Cells)
				10.9.5.1.2 Transfection
			10.9.5.2 Post Secretory Drug Loading
				10.9.5.2.1 Electroporation
				10.9.5.2.2 Sonication
				10.9.5.2.3 Freeze-Thaw Cycle
				10.9.5.2.4 Extrusion
				10.9.5.2.5 Co-Incubation (Drugs and Exosomes)
				10.9.5.2.6 Surfactant Treatment
				10.9.5.2.7 Dialysis
		10.9.6 Exosomes Applications in Cancer Treatment
			10.9.6.1 Small Molecule Chemotherapy Drugs
			10.9.6.2 Therapeutic Nucleic Acid
			10.9.6.3 Other Therapeutic Compounds
		10.9.7 Targeted Delivery of Exosomes
	10.10 Conclusion
	References