Polymeric nanoparticles for the treatment of solid tumors

Preface
Contents
About the Editors
Chapter 1: The Tumor Microenvironment
	1.1 Introduction
	1.2 Abnormal Cellular Constituents of the Tumour Microenvironment
		1.2.1 Pericytes
		1.2.2 Endothelial Cells
		1.2.3 Cancer-Associated Fibroblasts
		1.2.4 Tumour-Associated Macrophages
		1.2.5 Circulating Tumour Cells
		1.2.6 Exosomes
		1.2.7 Apoptotic Bodies
		1.2.8 Circulating Tumour DNA
		1.2.9 Inflammatory Mediators and Immune Cells
		1.2.10 Adipose Tissue
		1.2.11 Neuroendocrine System Involvement
		1.2.12 Tumour Microenvironment Components
	1.3 Abnormal Physiological Conditions of the Tumour Microenvironment
		1.3.1 pH
		1.3.2 Angiogenesis
			1.3.2.1 Vascular Endothelial Growth Factor Family
			1.3.2.2 Fibroblast Growth Factor and Fibroblasts
			1.3.2.3 Notch Signalling Pathway
			1.3.2.4 Transforming Growth Factor-β
		1.3.3 Extracellular Matrix
		1.3.4 Hypoxia
	1.4 Conclusion
	References
Chapter 2: Methods to Formulate Polymeric Nanoparticles
	2.1 Introduction
	2.2 Methods for Preparation of Polymeric Nanoparticle
		2.2.1 Nanoprecipitation
		2.2.2 Solvent Diffusion
		2.2.3 Emulsification Solvent Evaporation
		2.2.4 Interfacial Polymer Deposition
		2.2.5 Salting Out
		2.2.6 Supercritical Fluid Expansion
		2.2.7 Complex Coacervation
		2.2.8 Polymerization
		2.2.9 Ionotropic Gelation
		2.2.10 Spray Drying
		2.2.11 Phase Separation Technique
	2.3 Advanced Techniques for Preparation of Nanoparticles
		2.3.1 Ring Opening Polymerization
		2.3.2 Electro-Hydrodynamic Atomization
		2.3.3 Desolvation of Macromolecules
		2.3.4 Mussel-Inspired Chemistry for Polymerization
		2.3.5 Self-Polymerization
	2.4 Conclusion
	References
Chapter 3: Natural Polymers-Based Nanoparticles Targeted to Solid Tumors
	3.1 Introduction
	3.2 Formulation and Characteristics of Natural Polymers
		3.2.1 Polysaccharides
			3.2.1.1 Chitosan
				Formulation of Chitosan-Based Nanoparticles
			3.2.1.2 Hyaluronic Acid
				Formulations of Hyaluronic Acid-Based Nanoparticles
			3.2.1.3 Alginates
				Formulation of Alginate-Based Nanoparticles
			3.2.1.4 Dextran
				Formulation of Dextran-Based Nanoparticles
		3.2.2 Protein-Based Polymers
			3.2.2.1 Collagen
			3.2.2.2 Gelatin
				Formulation of Gelatin-Based Nanoparticles
			3.2.2.3 Albumin
				Formulation of Albumin-Based Nanoparticles
	3.3 Application of Polymeric Nanoparticles in Targeting Solid Tumors
		3.3.1 Active Targeting
		3.3.2 Passive Targeting
	3.4 Conclusion
	References
Chapter 4: Optimization of Physicochemical Properties of Polymeric Nanoparticles for Targeting Solid Tumors
	4.1 Introduction
	4.2 Physiology of Solid Tumors
	4.3 Physicochemical Properties of Polymeric Nanoparticles for Targeting Solid Tumors
		4.3.1 Size and Molecular Weight
		4.3.2 Hydrophobicity
		4.3.3 Surface Charge
		4.3.4 Crystallinity
		4.3.5 Biocompatibility
	4.4 Controlled Drug Release to Solid Tumors by Polymeric Nanoparticles
	4.5 Polymeric Nanoparticles for Stimuli-Responsive Targeted Drug Delivery
	4.6 Conclusion
	References
Chapter 5: Passive and Active Targeting for Solid Tumors
	5.1 Introduction
	5.2 Targeting Methods
		5.2.1 Passive Targeting
		5.2.2 Active Targeting
			5.2.2.1 Targeting of Cancer Cell
			5.2.2.2 Targeting of the Tumoral Endothelium
			5.2.2.3 Stimuli-Responsive Nanocarriers
				Internal Stimuli
				External Stimuli
	5.3 Surface-Modified Targeted Nanoplatforms
		5.3.1 Antibody, Enzymes and Proteins
		5.3.2 Aptamers
		5.3.3 Folate
		5.3.4 Transferrin
		5.3.5 Albumin
		5.3.6 Biotin
		5.3.7 Hyaluronic Acid
		5.3.8 Toxins
		5.3.9 Nucleic Acid
		5.3.10 Virus
		5.3.11 Affibodies
		5.3.12 Peptides and Polypeptides
		5.3.13 Miscellaneous
	5.4 Challenges
		5.4.1 Extravasation and the Enhanced Permeability and Retention Effect
		5.4.2 Tumor Microenvironment and Tumor Interstitium
		5.4.3 Physiological Barriers and pH
		5.4.4 Efficacy Versus Toxicity
		5.4.5 Translation from the In Vivo Model to the Human Model
		5.4.6 Metastasis
		5.4.7 Selection of Material for Designing Nanocarriers
	5.5 Preclinical and Clinical Intervention for Transposing to Market
	5.6 Commercialization and Government Regulations
	5.7 Conclusion
	References
Chapter 6: Polymeric Nanoparticles to Entrap Natural Drugs for Cancer Therapy
	6.1 Introduction
	6.2 Cancer
	6.3 Drugs of Natural Origin in Cancer Chemotherapy
	6.4 Role of Nanoparticles in Cancer Therapy
		6.4.1 Concept and Recent Development of Polymeric Nanoparticles Conjugated with target-specific ligands
			6.4.1.1 Active Targeting
			6.4.1.2 Passive Targeting
			6.4.1.3 Advances of Polymeric Nanoparticles in Conjugation with target-specific ligands
	6.5 Polymeric Nanocarriers in Guided Cancer Therapy
	6.6 Polymeric Nanoparticles Entrapping Drugs of Natural Origin
		6.6.1 Polymers and Drugs of Natural Origin
			6.6.1.1 Natural and Synthetic Polymers for the Preparation of Polymeric Nanoparticles
			6.6.1.2 Drugs of Natural Origin for Polymeric Nanoparticles in Cancer Therapeutics
		6.6.2 Mechanism of Drug Release for Polymeric Nanoparticles
			6.6.2.1 Diffusion Through Water-Filled Pores
			6.6.2.2 Diffusion Through the Polymeric Matrix
			6.6.2.3 Osmotic Pumping
			6.6.2.4 Erosion
		6.6.3 Clinical Applicability
		6.6.4 Recent Patents and Marketed Products Approved for Cancer Treatment
	6.7 Regulatory Compliance
	6.8 Perspective
	6.9 Conclusion
	References
Chapter 7: Polymeric Nanoparticles that Entrap Drug Combinations Targeted to Solid Tumors
	7.1 Introduction
	7.2 Types of Polymeric Nanoparticles
		7.2.1 Chitosan
		7.2.2 Gelatin
		7.2.3 Polyethylene Glycol
		7.2.4 Polyalkyl Cyanoacrylate
		7.2.5 Polyesters
		7.2.6 Polylactic Acid
		7.2.7 Polyglycolide
		7.2.8 Poly(Lactic-Co-Glycolic Acid)
		7.2.9 Polycaprolactone
		7.2.10 Polyvinyl Alcohol
	7.3 Advantages of Combinational Therapy Versus Single Drug in Nanosystems
	7.4 The Targeting Approach
		7.4.1 Passive Targeting of Polymeric Nanoparticles Entrapping Combination of Drugs
		7.4.2 Active Targeting of Polymeric Nanoparticles Entrapping Combination of Drugs
	7.5 Conclusion
	References
Chapter 8: Ligands Specific to Over-expressed Receptors in Solid Tumors
	8.1 Introduction
	8.2 Interventions for the Treatment of Solid Tumors
	8.3 Ideal Anticancer Drug Formulation
	8.4 Selective Targeting of Cancer Tissues
	8.5 Active Targeting or Smart Targeting
	8.6 Over-Expressed Receptors and Their Ligands in Solid Tumors
		8.6.1 Epidermal Growth Factor Receptor
		8.6.2 Folate Receptors
		8.6.3 Fibroblast Growth Factor Receptors
		8.6.4 Guanine Nucleotide Binding Protein Coupled Receptors
		8.6.5 Integrin Receptor
		8.6.6 Sigma Receptor
		8.6.7 Transferrin Receptor
		8.6.8 Vascular Endothelial Growth Factor Receptor
		8.6.9 Other Receptors
	8.7 Factors Affecting the Selection of Targeting Ligand
	8.8 Drug Delivery Systems, Drug Carriers and Smart Vehicles
	8.9 Conclusion
	References
Chapter 9: Ligand Targeted Polymeric Nanoparticles for Cancer Chemotherapy
	9.1 Introduction
	9.2 Mechanism of Ligand Decorated Nanoparticles Uptake by the Cell
	9.3 Ligand Directed Active Targeting for Cancer Treatment
		9.3.1 Small Molecule Directed Active Targeting Polymeric Nanoparticles
			9.3.1.1 Folic Acid
			9.3.1.2 Biotin
			9.3.1.3 Glycyrrhetinic Acid
		9.3.2 Polysaccharide Directed Active Targeting Polymeric Nanoparticles
			9.3.2.1 Galactosamine
			9.3.2.2 Hyaluronic Acid
		9.3.3 Proteins Directed Active Targeting Polymeric Nanoparticles
			9.3.3.1 Transferrin
			9.3.3.2 Lactoferrin
			9.3.3.3 Epidermal Growth Factor
			9.3.3.4 Lectin
			9.3.3.5 Monoclonal Antibody
	9.4 Conclusion
	References
Chapter 10: Polymeric Nanoparticles as Theranostics for Targeting Solid Tumors
	10.1 Introduction
	10.2 Theranostic Polymeric Nanomedicine for the Treatment of Solid Tumor Cancer
		10.2.1 Polymeric Gold Nanoparticles
		10.2.2 Polymeric Micelles
		10.2.3 Polymeric Superparamagnetic Nanoparticles
		10.2.4 Quantum Dots-Loaded Polymeric Nanoparticles
		10.2.5 Polymeric Nanoparticles Containing Dendrimers
		10.2.6 Polymeric Nanoparticles Along with Carbon Nanotubes
		10.2.7 Miscellaneous Carriers
			10.2.7.1 Polymeric Liposomes
			10.2.7.2 Polymersomes
	10.3 Polymeric Nanoparticles in Clinical Trials
	10.4 Conclusion
	References
Chapter 11: Oral Delivery of Polymeric Nanoparticles for Solid Tumors
	11.1 Introduction
	11.2 Gastrointestinal Tract Physiology
	11.3 Physiological Barriers as Hurdles for the Oral Delivery of Chemotherapeutics
		11.3.1 Biochemical Barrier
		11.3.2 Mucosal Barrier
		11.3.3 Cellular Permeability Barrier
	11.4 Biopolymeric Nano-Drug Delivery Systems for Oral Administration of Chemotherapeutics
		11.4.1 Protein-Based Biopolymers
			11.4.1.1 Gelatin
			11.4.1.2 Collagen
		11.4.2 Poly-Amino and Poly-Ester Based Biopolymers
			11.4.2.1 Poly(Lactic-Co-Glycolic Acid)
			11.4.2.2 Polyglutamic Acid
		11.4.3 Polysaccharide-Based Biopolymers
			11.4.3.1 Chitosan
			11.4.3.2 Pullulan
			11.4.3.3 Hyaluronic Acid
			11.4.3.4 Alginates
	11.5 Conclusion
	References
Chapter 12: Polymeric Nanoparticles to Target Glioblastoma Tumors
	12.1 Introduction
	12.2 Glioblastoma
	12.3 Advances in the Development of Novel Therapeutics for Glioblastoma
	12.4 Drug Delivery to the Brain
	12.5 Polymeric Nanoparticles for Targeting Glioblastoma
	12.6 Peptide-Receptor as a Dual-Targeting Drug Delivery Approach
	12.7 Dual-Targeting of Both Glioma and Neovascular Cells
	12.8 Aptamer-Peptide Conjugates as a Dual-Targeting Delivery System
	12.9 Routes of Administration of Nanoparticles in the Treatment of Malignant Gliomas
	12.10 Challenges Related to Nanotherapy of Malignant Gliomas
		12.10.1 Reticulo Endothelial System
		12.10.2 Renal System
		12.10.3 Blood Brain Barrier
		12.10.4 Pathophysiological Barriers in Cancer
		12.10.5 Multidrug Resistance
	12.11 Conclusion
	References
Chapter 13: Polymeric Nanoparticles to Target Lung Cancer
	13.1 Introduction
		13.1.1 Pathology of Lung Cancer
	13.2 Modalities for the Treatment of Lung Cancer and Limitations
		13.2.1 Photodynamic Therapy
		13.2.2 Surgery
		13.2.3 Chemotherapy
		13.2.4 Radiation Therapy
	13.3 Advances in Drug Delivery Systems for the Diagnosis of Lung Cancer
	13.4 Polymer-Based Nanoparticulate System for the Management of Lung Cancer
		13.4.1 Poly(Lactic-Co-Glycolic Acid) Based Nanoparticles
		13.4.2 Polylactic Acid Based Nanoparticles
		13.4.3 Cellulose Acetate Phthalate-Based Nanoparticles
		13.4.4 Polycaprolactone-Based Nanoparticles
		13.4.5 Hyaluronic Acid Nanoparticles
		13.4.6 Other
	13.5 Benefits of Drug Delivery Systems for the Management of Lung Cancer
	13.6 Recent Patents and Clinical Trials on Drug Delivery Systems for Lung Cancer
	13.7 Conclusion
	References
Chapter 14: Polymer-Based Nanoplatforms for Targeting Breast Cancer
	14.1 Introduction
		14.1.1 Breast Cancer Types and Cellular Targets
		14.1.2 Types of Polymeric Materials and Nanoplatforms
		14.1.3 Current Trends
	14.2 Strategies for Choosing Polymeric Nanomaterials
	14.3 Polymeric Nanoplatforms for Cargo Delivery to Tumor Cells
		14.3.1 Polymeric Nanoparticles
		14.3.2 Polymer-Based Nanocomposites
		14.3.3 Polymeric Nanoplexes
		14.3.4 Surface-Modified Nanoplatforms
		14.3.5 Antibodies and Immunological Agents
		14.3.6 Aptamers
		14.3.7 Small Interfering RNA and Messenger RNA
		14.3.8 Miscellaneous
	14.4 Polymeric Nanoparticles and Nanomaterials-Based Theranostic Strategies
	14.5 Toxicological Perspectives of Polymeric Nanoplatforms
	14.6 Conclusion
	References
Chapter 15: pH-Sensitive Polymeric Nanoparticles for Cancer Treatment
	15.1 Introduction
	15.2 Mechanism of Action of pH-Sensitive Polymeric Nanoparticles
	15.3 Designing of pH-Sensitive Polymeric Nanoparticles
		15.3.1 Charge Shifting Polymers
		15.3.2 Acid Labile Linkers as Pendant Functionality
		15.3.3 Acid Linkers to Produce Cross-Linked Particles
	15.4 Characteristics of Polymers Used for pH-Sensitive Polymeric Nanoparticles
	15.5 Application of pH-Sensitive Polymeric Nanoparticles in the Treatment of Cancer
		15.5.1 Change of Hydrophobic Property to Hydrophilic Property by Transfer of Charge
		15.5.2 Change of Hydrophilic Property to Hydrophobic Property by Transfer of Charge
		15.5.3 pH-Responsive Polymers with Acid Labile Linkages
		15.5.4 Crosslinking
	15.6 Conclusion
	References
Chapter 16: Polymeric Nanoplatforms for the Targeted Treatment of Prostate Cancer
	16.1 Introduction
	16.2 The Emerging Era of Polymeric Nanoparticles
	16.3 Surface Engineered Polymeric Nanoparticles for Prostate Cancer
		16.3.1 Passive Targeting
		16.3.2 Ligand-Based Targeting
	16.4 Polymeric Nanoparticles for Targeting Prostate Cancer
		16.4.1 Solid Dispersion of Polymeric Nanoparticles
		16.4.2 Conjugated Polymeric Nanoparticles
		16.4.3 Polymer-Lipid Hybrid Systems
		16.4.4 Polymeric Micelles
		16.4.5 Polyplexes
		16.4.6 Miscellaneous Polymeric Nanoparticles
	16.5 Stimuli-Responsive Polymeric Nanoparticles
		16.5.1 pH-Responsive Polymeric Nanoparticles
		16.5.2 Enzyme-Responsive Polymeric Nanoparticles
		16.5.3 Ultrasound-Triggered Polymeric Nanoparticles
		16.5.4 Dual-Responsive Polymeric Platforms
	16.6 Advances in Polymeric Nanoparticles for Prostate Cancer
		16.6.1 Polymer-Based Superparamagnetic Nanoparticles
		16.6.2 Polymeric Nanoparticles Bearing Radionuclide,  Magnetic Resonance Imaging Agents and Metal Nanoparticles
		16.6.3 Miscellaneous Advanced Polymeric Platform
	16.7 Challenges
	16.8 Conclusion
	References
Chapter 17: Cellular Internalization and Toxicity of Polymeric Nanoparticles
	17.1 Introduction
	17.2 Factors Affecting Cellular Internalization of Polymeric Nanoparticles in Tumors
		17.2.1 Particle Size
		17.2.2 Particle Shape
		17.2.3 Surface Charge
		17.2.4 Conjugating Ligands
	17.3 Toxicity of Nanoparticles
	17.4 Conclusion
	References
Chapter 18: Prospects and Challenges in the Treatment of Solid Tumors
	18.1 Introduction
	18.2 Current Treatment of Solid Tumors
		18.2.1 Chemotherapy
		18.2.2 Radiotherapy
			18.2.2.1 Types of radiotherapy
		18.2.3 Surgery
	18.3 Advantages and Disadvantages of Treatments
		18.3.1 Advantages
		18.3.2 Disadvantages
	18.4 Challenges
		18.4.1 Immune Evasion Mechanisms in Tumors
		18.4.2 Clinical Implementation of Next-Generation Sequencing Technologies
		18.4.3 Conducting Biomarker-Driven Clinical Trials
		18.4.4 Tumor Heterogeneity and Resistance
	18.5 Perspective
		18.5.1 Better Classification of Tumors
		18.5.2 Simplification and Acceleration of the Drug Development System
		18.5.3 Design of Trials
		18.5.4 Role of Nano-Formulation
	18.6 Conclusion
	References
Index