Nanoparticulate Drug Delivery Systems: Strategies, Technologies, and Applications -- Contents -- Preface -- Contributors -- 1 Tumor-Targeted Nanoparticles: State-of-the-Art and Remaining Challenges -- 1.1 INTRODUCTION -- 1.2 FUNCTIONS OF NANOPARTICLES -- 1.3 TUMOR-TARGETED NANOPARTICLES -- 1.3.1 Passive Targeting -- 1.3.2 Active Targeting -- 1.3.3 Target-Activated Systems -- 1.4 REMAINING CHALLENGES IN THE DEVELOPMENT OF TUMOR-TARGETED NANOPARTICLES -- 1.4.1 NP Stability -- 1.4.2 Heterogeneous Tumor Vasculature -- 1.4.3 NP Distribution in Tumors -- 1.4.4 Regulatory Considerations -- 1.5 FUTURE PERSPECTIVES -- 1.5.1 In Vitro Models -- 1.5.2 In Vivo Models -- 1.5.3 New Targets -- 1.5.4 New Therapeutic Agents -- Acknowledgments -- REFERENCES -- 2 Applications of Ligand-Engineered Nanomedicines -- 2.1 INTRODUCTION -- 2.1.1 Nanoparticulate Drug Delivery -- 2.1.2 Engineered Nanoparticulate Drug Delivery -- 2.2 LIGAND-MEDIATED DELIVERY -- 2.2.1 Antibodies -- 2.2.2 Peptides and Proteins -- 2.2.3 Sugars and Polysaccharides -- 2.2.4 Small Molecule Chemicals -- 2.3 CURRENT CHALLENGES IN CLINICAL DEVELOPMENT OF LIGAND-MODIFIED NANOMEDICINE -- 2.3.1 Nonclinical and Clinical Studies -- 2.3.2 Challenges and Future Perspectives -- 2.4 CONCLUSIONS -- Acknowledgments -- REFERENCES -- 3 Lipid Nanoparticles for the Delivery of Nucleic Acids -- 3.1 INTRODUCTION -- 3.2 BARRIERS TO SYSTEMIC GENE DELIVERY -- 3.2.1 Extracellular Barriers -- 3.2.2 Intracellular Barriers -- 3.3 COMPONENTS OF LNPs -- 3.3.1 Cationic Lipid -- 3.3.2 Neutral Lipid -- 3.3.3 Anionic Lipid -- 3.3.4 PEG-Lipid Conjugates -- 3.4 FORMULATIONS OF THE LNP FOR NUCLEIC ACIDS ENCAPSULATION -- 3.4.1 Self-Assembly -- 3.4.2 Detergent Dialysis -- 3.4.3 Nanometric Calcium Phosphate/siRNA Precipitation -- 3.5 ORGAN-SPECIFIC DELIVERY OF NUCLEIC ACIDS WITH LNPs -- 3.5.1 Brain-Targeted Delivery.

3.5.2 Liver-Targeted Delivery -- 3.5.3 Lung-Targeted Delivery -- 3.5.4 Kidney-Targeted Delivery -- 3.6 CURRENT CHALLENGES TO THE DEVELOPMENT OF LNPs -- 3.7 FUTURE PERSPECTIVES -- Acknowledgments -- REFERENCES -- 4 Photosensitive Liposomes as Potential Targeted Therapeutic Agents -- 4.1 INTRODUCTION -- 4.2 EXPERIMENTAL PROCEDURES -- 4.2.1 Materials -- 4.2.2 Synthesis of 1-Bromo-3-hexadecylthiobenzene (1) -- 4.2.3 Synthesis of 9-[3-Hexadecylthiophenyl] anthracene (2) -- 4.2.4 Synthesis of 9-[3-Hexadecyl-3'-cyanobenzylsulfonium] phenylanthracene Trifluoromethanesulfonate (C16-An-PAG) (3) -- 4.2.5 Liposome Preparation -- 4.2.6 Dynamic Light Scattering -- 4.2.7 Photoexcitation Method -- 4.2.8 Calcium Ion Release Assay -- 4.2.9 Negative Stain Transmission Electron Microscopy -- 4.2.10 Animal Studies -- 4.3 RESULTS AND DISCUSSION -- 4.3.1 DOPE:LysoPlsC Liposomes Using C16-An-PAG as a Photosensitizer -- 4.3.2 PPlsC Liposomes Using Bchl a as a Photosensitizer -- 4.3.3 Folate Receptor (FR)-Targeted DPPlsC Liposomes Using AlPcS4-4 as a Photosensitizer -- 4.4 CONCLUSIONS -- 4.5 PROSPECTS FOR LIGHT-ACTIVATED LIPOSOMAL DRUG DELIVERY -- Acknowledgments -- REFERENCES -- 5 Multifunctional Dendritic Nanocarriers: The Architecture and Applications in Targeted Drug Delivery -- 5.1 RECENT ADVANCES IN DENDRITIC NANOMATERIALS -- 5.2 EFFECTS OF DENDRITIC ARCHITECTURES ON BIOLOGICAL SYSTEMS -- 5.2.1 Structure-Related Toxicity and Biodistribution -- 5.2.2 Mechanisms for Cell Entry of Dendrimers -- 5.2.3 Multivalent Interactions -- 5.3 FUNCTIONALIZATION OF DENDRITIC STRUCTURES VIA SURFACE MODIFICATION -- 5.4 DENDRIMER-BASED THERAPEUTIC AND DIAGNOSTIC APPROACHES -- 5.4.1 Delivery of Anticancer Drugs -- 5.4.2 Gene Delivery -- 5.4.3 Imaging -- 5.5 DENDRON-BASED HYBRID NANOMATERIALS -- 5.6 FUTURE PERSPECTIVES -- REFERENCES.

6 Chitosan-Based Nanoparticles for Biomedical Applications -- 6.1 CHITOSAN AS A BIOPOLYMER -- 6.2 CHITOSAN NANOPARTICLES FOR IMAGING -- 6.2.1 Optical Imaging -- 6.2.2 Magnetic Resonance (MR) Imaging -- 6.2.3 Computed Tomography (CT) Imaging -- 6.2.4 Positron Emission Tomography (PET) Imaging -- 6.2.5 Ultrasound (US) Imaging -- 6.3 CHITOSAN NANOPARTICLES FOR THERAPY -- 6.3.1 Drug Delivery -- 6.3.2 Gene Delivery -- 6.3.3 Photodynamic Therapy -- 6.4 PROMISES, LIMITATIONS, AND FUTURE PERSPECTIVES OF CHITOSAN NANOPARTICLES -- REFERENCES -- 7 Polymer-Drug Nanoconjugates -- 7.1 INTRODUCTION -- 7.2 CURRENT STATUS OF NANOENCAPSULATES AND POLYMER-DRUG CONJUGATES -- 7.2.1 Nanoencapsulates -- 7.2.2 Polymer-Drug Conjugates -- 7.3 NANOCONJUGATES: DESIGN AND SYNTHESIS -- 7.3.1 Design and General Consideration -- 7.3.2 Synthesis of Cpt-PLA Nanoconjugates -- 7.3.3 Synthesis of Ptxl-PLA (Dtxl-PLA) Nanoconjugates -- 7.3.4 Synthesis of Doxo-PLA Nanoconjugates -- 7.4 NANOCONJUGATES: FORMULATION AND POTENTIAL APPLICATION -- 7.4.1 Formulation -- 7.4.2 Theranostic Nanoconjugates -- 7.4.3 Nanoconjugates Against Other Diseases -- 7.5 CONCLUSIONS AND OUTLOOK -- Acknowledgments -- REFERENCES -- 8 Nanocrystals Production, Characterization, and Application for Cancer Therapy -- 8.1 INTRODUCTION -- 8.2 NANOCRYSTAL PRODUCTION -- 8.2.1 Top-Down Approach -- 8.2.2 Bottom-Up Approach -- 8.2.3 Combined Approach -- 8.3 PARTICLE STABILIZATION -- 8.4 PARTICLE CHARACTERIZATION -- 8.4.1 Particle Size -- 8.4.2 Surface Charge -- 8.4.3 Crystallinity -- 8.4.4 Dissolution -- 8.5 NANOCRYSTALS FOR CANCER THERAPY -- 8.6 FUTURE PERSPECTIVES -- Acknowledgments -- REFERENCES -- 9 Clearance of Nanoparticles During Circulation -- 9.1 INTRODUCTION -- 9.2 NANOPARTICLE-BASED DRUG CARRIERS IN CANCER THERAPY -- 9.2.1 Nanoparticle-Based Drug Carriers -- 9.2.2 Tumor Targeting Strategies.

9.3 BIOLOGICAL CLEARANCE OF NANOPARTICLES -- 9.3.1 Blood Clearance -- 9.3.2 Organ Filtrations -- 9.4 STRATEGIES TO MINIMIZE THE BIOLOGICAL CLEARANCE OF NANOPARTICLES -- 9.4.1 Chemical Cross-Linking -- 9.4.2 Surface Modification -- 9.4.3 Control of the Size, Shape, and Deformability of Nanoparticles -- 9.5 FUTURE PERSPECTIVES -- REFERENCES -- 10 Drug Delivery Strategies for Combating Multiple Drug Resistance -- 10.1 INTRODUCTION -- 10.2 PATHWAYS TO DRUG RESISTANCE -- 10.2.1 Resistance of the Tumor Microenvironment -- 10.2.2 Cellular Resistance -- 10.2.3 Perspective on Drug Resistance -- 10.3 COMBATING MDR -- 10.3.1 Bypassing MDR by Endocytosis -- 10.3.2 Co-Delivery of Drugs with Other Compounds -- 10.3.3 Stimuli-Based Methods -- 10.4 FUTURE PERSPECTIVES -- Acknowledgments -- REFERENCES -- 11 Intracellular Trafficking of Nanoparticles: Implications for Therapeutic Efficacy of the Encapsulated Drug -- 11.1 INTRODUCTION -- 11.2 PATHWAYS OF CELLULAR ENTRY -- 11.2.1 Endocytosis: Many Different Versions -- 11.2.2 Factors Affecting Nanoparticle Uptake into Cells -- 11.2.3 Targeting Ligand-Mediated Cellular Entry of Nanoparticles -- 11.3 INTRACELLULAR FATE OF INTERNALIZED NANOPARTICLES -- 11.3.1 Organelle Targeting -- 11.3.2 Exocytosis of Nanoparticles -- 11.4 IN-DEPTH ELUCIDATION OF INTRACELLULAR TRAFFICKING EVENTS ENTAILS HIGH RESOLUTION IMAGING TECHNIQUES -- 11.5 FUTURE PERSPECTIVES -- REFERENCES -- 12 Toxicological Assessment of Nanomedicine -- 12.1 INTRODUCTION -- 12.2 SAFETY OF COMMONLY USED NANOCONSTRUCTS IN NANOMEDICINE -- 12.2.1 Liposomes -- 12.2.2 Polymer Conjugates and Polymeric Micelles -- 12.2.3 Dendrimers -- 12.2.4 Carbon Nanotubes -- 12.2.5 Silica NPs -- 12.2.6 Metal-Based NPs -- 12.3 EVALUATION OF NANOMATERIAL TOXICITY -- 12.3.1 Characterization -- 12.3.2 Absorption, Distribution, Metabolism, and Excretion (ADME).

12.3.3 Acute and Chronic Toxicity -- 12.3.4 Genotoxicity -- 12.3.5 Carcinogenicity -- 12.3.6 Reproductive and Developmental Toxicity -- 12.4 CONCLUSIONS -- Acknowledgments -- REFERENCES -- Index.