Drug Delivery to Tumors: Recent Strategies and Techniques

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Drug Delivery to Tumors: Recent Strategies and Techniques
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Preface
Contents
About the Editors
1. Cancer Biology and Microenvironment
	1.1 Formation of Tumor Blood Vessel
		1.1.1 Vasculogenesis
		1.1.2 Sprouting Angiogenesis
		1.1.3 Vascular Mimicry
		1.1.4 Intussusception
	1.2 Metabolism Reprogramming
		1.2.1 Glucose Metabolism
		1.2.2 Amino Acid Metabolism
		1.2.3 Fatty Acid Metabolism
	1.3 Tumor Immunity
		1.3.1 The Tumor-Antagonizing Immune Cells in TME
		1.3.2 The Tumor-Promoting Immune Cells in TME
		1.3.3 The Controversial Immune Cell Type in Tumors: B Cells
		1.3.4 The cGAS-STING Pathway
	1.4 Endoplasmic Reticulum Stress and Unfolded Protein Response in Tumor
		1.4.1 The Three UPR Branches
		1.4.2 The Role of ER Stress and UPR in Cell Survival
		1.4.3 The Role of ER Stress and UPR in Angiogenesis
		1.4.4 The Role of ER Stress and UPR in Metastasis
	1.5 Tumor Hypoxia
		1.5.1 Regulation of HIF
		1.5.2 Hypoxia and HIF in Tumor Angiogenesis
		1.5.3 Hypoxia and HIF in Tumor Metabolic Reprogramming
		1.5.4 Hypoxia and HIF in Tumor Immunity
	1.6 Conclusions
	References
2. Development and Advantages of Drug Delivery Systems
	2.1 Introduction
	2.2 The History of Drug Delivery Technologies
	2.3 The Third-Generation Drug Delivery Technologies
		2.3.1 Target DDS
		2.3.2 Sustained-Release DDS
		2.3.3 Pulsatile Release DDS
		2.3.4 Feedback-Regulated DDS
	2.4 Delivery Strategies for Biologics
		2.4.1 DDSs for Proteins and Peptides
		2.4.2 DDSs for Nucleotide Drugs
	2.5 Different Components of DDS
	2.6 Concluding Remarks
	References
3. Drug Delivery Strategies That Target Tumors
	3.1 Passive Targeting and Irrational Application of EPR Effect
		3.1.1 Bradykinin
		3.1.2 Nitric Oxide
		3.1.3 Vascular Endothelial Growth Factor
		3.1.4 Tumor Necrosis Factor-α
	3.2 Active Targeting
		3.2.1 Folate Receptor
		3.2.2 Transferrin Receptor
		3.2.3 Epidermal Growth Factor Receptor Family
	3.3 Emerging Strategy for Tumor Targeting
		3.3.1 Hypoxia Response Nanocarriers
		3.3.2 pH-Sensitive Nanoparticles
		3.3.3 External Stimulus-Responsive Nanoparticles
	3.4 Conclusions
	References
4. Combined Therapy in Cancer Treatment
	4.1 Introduction
	4.2 Chemical and Nucleic Acid Drugs
		4.2.1 Combination of Chemical and Nucleic Acids Drug for Improved Apoptosis
		4.2.2 Combination of Chemotherapy and Nucleic Acids for Overcoming Multidrug Resistance (MDR)
	4.3 Chemo-Immunotherapy
	4.4 Combined Therapy of Immunotherapy with Photothermal Therapy (PTT) and Photodynamic Therapy (PDT)
	4.5 Conclusion
	References
5. Prodrug Nanocarrier
	5.1 Introduction
	5.2 Construction of Prodrug Nanocarriers
		5.2.1 Drug–Drug
		5.2.2 Drug-Monomer/Polymer
		5.2.3 Drug-Carrier Nanocomposites
			5.2.3.1 Physical Entrapment
			5.2.3.2 Chemical Conjugation
	5.3 Stimuli-Responsive Strategies for Prodrug Nanocarriers
		5.3.1 Endogenous Stimuli
			5.3.1.1 pH-Sensitive Prodrug Nanocarriers
			5.3.1.2 Redox-Responsive Prodrug Nanocarrier
			5.3.1.3 Enzyme-Responsive Prodrug Nanocarriers
		5.3.2 Exogenous Stimuli
			5.3.2.1 Light-Responsive Prodrug Nanocarriers
			5.3.2.2 Ultrasound-Responsive Prodrug Nanocarriers
			5.3.2.3 Thermoresponsive Prodrug Nanocarriers
			5.3.2.4 Magnetism-Responsive Prodrug Nanocarriers
		5.3.3 Multiresponsive Prodrug Nanocarrier
	5.4 Conclusion and Future Perspectives
	References
6. Smart Drug Delivery Vehicle
	6.1 Endogenous Stimulation
		6.1.1 pH-Responsive Vehicles
		6.1.2 Redox-Responsive Vehicles
		6.1.3 ATP-Responsive Vehicles
		6.1.4 Enzyme-Responsive Vehicles
		6.1.5 Hypoxia-Responsive Vehicles
		6.1.6 Glucose-Responsive Vehicles
	6.2 Exogenous Stimuli
		6.2.1 Light-Responsive Vehicles
		6.2.2 Heat-Responsive Vehicles
		6.2.3 Magnet-Responsive Vehicles
		6.2.4 Electric-Responsive Vehicles
		6.2.5 Ultrasound-Responsive Vehicles
	References
7. Cell Derived/Bionic-Drug Delivery Vehicles
	7.1 Introduction
	7.2 DDSs Based on Cell Membranes
		7.2.1 DDSs Construction
			7.2.1.1 Extraction and Separation of Membranes
			7.2.1.2 Isolation of Exosomes
			7.2.1.3 Separation and Extraction Outer-Membrane Vesicles (OMVs)
		7.2.2 Drug Loading
			7.2.2.1 Co-extrusion
			7.2.2.2 Sonication
			7.2.2.3 Microfluidic Electroporation
			7.2.2.4 Spontaneous Formation by Electrostatic Attractions
			7.2.2.5 Bath Sonication
			7.2.2.6 Other Methods
	7.3 Advantages of Cell Membrane-Coated NPs
		7.3.1 Stability
		7.3.2 Immune Evasion and Long Circulation
		7.3.3 Targeting Ability
		7.3.4 Easy to Obtain
		7.3.5 Other Advantages
	7.4 Applications
		7.4.1 RBC Membrane
		7.4.2 Platelet Membrane
		7.4.3 Cancer Cell Membrane
		7.4.4 Immune Cell Membrane
		7.4.5 Mesenchymal Stem Cell Membrane (MSCs)
		7.4.6 Bacterial Membrane (Outer Membrane Vesicle (OMV))
		7.4.7 Exosomes
		7.4.8 Antibacterial Applications of Biofilms
	7.5 Challenges
	7.6 Conclusion
	References
8. Cellular Drug Delivery Vehicle
	8.1 Introduction
	8.2 Stem Cells
	8.3 Monocytes/Macrophages
	8.4 T Cells
	8.5 Red Blood Cell (RBC) Carrier
	8.6 Bacteria Carrier
	8.7 Dendritic Cells
	References
9. Nanocrystal Technology
	9.1 Introduction
	9.2 Preparation of Nanocrystals
		9.2.1 Bottom-Up Techniques
			9.2.1.1 Supercritical Fluid Technique
			9.2.1.2 Precipitation Technique
		9.2.2 Top-Down Techniques
			9.2.2.1 Media Milling
			9.2.2.2 High-Pressure Homogenization (HPH)
		9.2.3 Combination Techniques
	9.3 Administration Routes of Drug Nanocrystals
		9.3.1 Oral Drug Delivery
		9.3.2 Dermal Drug Delivery
		9.3.3 Pulmonary Drug Delivery
		9.3.4 Ocular Drug Delivery
		9.3.5 Parenteral Drug Delivery
		9.3.6 Targeted Drug Delivery
	9.4 Status of Drug Nanocrystals in the Market and Clinical Trials
	9.5 Researches on Drug Nanocrystals in the Tumor Target Delivery
		9.5.1 Passive Targeting
		9.5.2 Specific Organs Targeting
		9.5.3 Cell-Based Targeting
	9.6 Summary and Future Perspectives
	References
10. Application of Microneedles in Antitumor Therapy
	10.1 Introduction
	10.2 Classification and Characteristics of MNs
		10.2.1 Solid MNs
		10.2.2 Coated MNs
		10.2.3 Hollow MNs
		10.2.4 Dissolving MNs
		10.2.5 Hydrogel-Forming MNs
	10.3 Preparation Methods of MNs
		10.3.1 Solid MNs
		10.3.2 Coated MNs
		10.3.3 Hollow MNs
		10.3.4 Dissolving MNs
		10.3.5 Hydrogel MNs
	10.4 Characteristics of MNs
		10.4.1 MNs for Drug Loading
			10.4.1.1 Small Molecular Drugs
			10.4.1.2 Macromolecular Drugs
			10.4.1.3 Nanoparticles
		10.4.2 Mechanical Strength
		10.4.3 Drug Release and Distribution
			10.4.3.1 Rapid Drug Release
			10.4.3.2 Sustained Drug Release
			10.4.3.3 Stimulus-Responsive Drug Release
			10.4.3.4 Drug Penetration and Distribution
	10.5 The Application of MNs for Cancer Therapy
		10.5.1 The Application of MNs for Chemotherapy
		10.5.2 The Application of MNs for Phototherapy
		10.5.3 The Application of MNs for Immunotherapy
			10.5.3.1 Cancer Vaccine
			10.5.3.2 Antibody Immunotherapy
		10.5.4 The Application of MNs for Combination Cancer Therapy
			10.5.4.1 Chemo-photothermal Therapy
			10.5.4.2 Photothermal-immunotherapy
	References