Part A Overview, molecular pathways and conventional therapy of pancreatic cancer 1. An overview of the anatomy, physiology, and pathology of pancreatic cancer Farzad Rahmani and Amir Avan 1.1 Pancreas anatomy 1.2 Pancreas physiology 1.2.1 Endocrine pancreas 1.2.2 Exocrine pancreas 1.3 Pancreas cancer pathology 1.3.1 Pathology of the exocrine neoplasms of the pancreas 1.3.2 Pathology of the endocrine neoplasms of pancreas 1.4 Conclusion References 2. Different combination therapies pertaining to pancreatic cancer Zahra Salmasi, Parisa Saberi-Hasanabadi, Hamidreza Mohammadi and Rezvan Yazdian-Robati 2.1 Introduction 2.2 Carrier-free combination therapy in pancreatic cancer treatment 2.3 Nanoparticle-mediated combination therapy in pancreatic cancer treatment 2.3.1 Metal and metal oxide nanoparticles 2.3.2 Nonmetallic nanoparticles 2.3.3 Polymeric nanoparticles 2.3.4 Lipid-based nanoparticle 2.4 Combination treatment with chimeric antigen receptor T cells and oncolytic viruses 2.5 Compounds of natural origin and combination therapy in pancreatic cancer treatment 2.5.1 The role of bioactive compounds of natural origin based on nano-formulation in inhibiting the proliferation of pancreatic cancer cells 2.6 Conclusions and perspectives References Part B Application of various nanocarriers for the management of pancreatic cancer 3. Potential application of nanotechnology in the treatment and overcoming of pancreatic cancer resistance Shwetapadma Dash, Sonali Sahoo and Sanjeeb Kumar Sahoo 3.1 Introduction 3.2 Current therapeutics for pancreatic cancer 3.2.1 Conventional therapies 3.2.2 Targeted therapies 3.3 Drug resistance as a pitfall 3.3.1 Role of drug uptake and drug metabolism pathways 3.3.2 Role of key signaling networks 3.3.3 Tumor microenvironment 3.3.4 Cancer stem cells and epithelial to mesenchymal transition as regulators 3.3.5 Other miscellaneous pathways and factors 3.4 Nanotechnology as a therapeutic window 3.4.1 Nanotherapeutic strategies using chemotherapeutic drugs 3.4.2 Nanotherapeutics-based approaches for targeting drug resistance 3.4.3 Nanotherapeutics-based approaches for targeting tumor microenvironment 3.4.4 Pro- and antiapoptotic genes: evasion and overexpression 3.4.5 Nanotherapeutic strategies for targeting cancer stem cells 3.4.6 Nanoparticles as delivery vehicles for RNA interference inhibitors 3.4.7 Nanomaterials for early detection and advancing pancreatic cancer imaging for pancreatic cancer 3.5 Conclusion References 4. Application of hydrogel-based drug delivery system for pancreatic cancer Naomi Sanjana Sharath, Ranjita Misra and Jyotirmoy Ghosh 4.1 Introduction 4.2 Pancreatic cancer 4.3 Physiology 4.3.1 Treatment 4.4 Limitations 4.5 Hydrogels 4.6 Types of polymers used in hydrogels 4.6.1 Natural polymers 4.6.2 Synthetic polymers 4.7 Preparation of hydrogels 4.7.1 Bulk polymerization 4.7.2 Solution polymerization 4.7.3 Optical polymerization 4.7.4 Enzymatic polymerization 4.8 Types of some common hydrogels 4.8.1 Injectable hydrogels 4.8.2 Temperature-sensitive hydrogels 4.8.3 pH-sensitive hydrogels 4.8.4 Photosensitive hydrogels 4.8.5 Electrosensitive hydrogels 4.9 Applications of hydrogels against pancreatic cancer 4.10 Diagnosis 4.10.1 Therapy 4.10.2 Organoid development for cancer treatment 4.11 Conclusion and future outlook References 5. Liposome- and noisome-based drug delivery for pancreatic cancer Rezvan Yazdian-Robati, Seyedeh Melika Ahmadi, Faranak Mavandadnejad, Pedram Ebrahimnejad, Shervin Amirkhanloo and Amin Shad Abbreviations 5.1 Introduction 5.2 Liposome-based drug delivery 5.2.1 Components and structure of liposome 5.3 Liposomal drug delivery platforms for pancreatic cancer 5.3.1 Liposome-drugs to treat pancreatic cancer 5.3.2 Liposome-naturally derived bioactive compounds to treat pancreatic cancer 5.3.3 Liposomal delivery of CRISPR/Cas9 to treat PC 5.4 Targeted nanoliposomes for pancreatic cancer treatment 5.4.1 Transporter-targeted liposome for pancreatic cancer therapy 5.4.2 Antibody-decorated liposomes for pancreatic cancer 5.4.3 Peptide-decorated liposome 5.4.4 Carbohydrate-decorated liposomes 5.5 Stimuli-responsive liposomal nano-formulations for pancreatic cancer 5.5.1 pH-sensitive liposomes 5.5.2 Magnetic sensitive and ultrasound liposomes 5.5.3 Thermo-sensitive liposomes 5.6 Clinical studies of liposomal formulation for pancreatic cancer treatment 5.7 Noisome-based drug delivery 5.7.1 Structure and components of niosomes 5.7.2 Noisome drug delivery for pancreatic cancer treatment 5.8 Conclusion Declaration of competing interest References 6. Micelles-based drug delivery for pancreatic cancer Sanjay Ch, Tarun Kumar Patel, Swati Biswas and Balaram Ghosh 6.1 Introduction 6.2 Micellar uptake mechanism 6.2.1 Endocytosis 6.2.2 Phagocytosis 6.2.3 Pinocytosis 6.2.4 Macropinocytosis 6.3 Polymeric micelles and their types 6.3.1 Conventional polymeric micelles 6.3.2 Polymeric micelles based on functionalities 6.4 Pancreatic cancertargeting sites for micelles 6.4.1 Epidermal growth factor 6.4.2 Transferrin 6.4.3 Urokinase plasminogen activator receptor 6.4.4 Fucosylated antigen 6.4.5 Integrins 6.5 Small interfering RNA-loaded micelles for pancreatic cancer therapy 6.6 Polymeric micelles in clinical studies for pancreatic cancer 6.7 Conclusion References 7. Theranostic nanoparticles in pancreatic cancer Sania Ghobadi Alamdari, Reza Mohammadzadeh, Behzad Baradaran, Mohammad Amini, Ahad Mokhtarzadeh and Fatemeh Oroojalian 7.1 Introduction 7.2 Metal nanoparticles 7.2.1 Gold nanoparticles 7.2.2 Iron oxide nanoparticles 7.2.3 Silica nanoparticles 7.2.4 Other metal nanoparticles 7.3 Polymeric nanoparticles 7.3.1 Natural polymer nanoparticles 7.3.2 Synthetic polymer nanoparticles 7.4 Carbon nanoparticles 7.5 Conclusion References 8. Recent advances in nanocarriers for pancreatic cancer therapy Shalini Preethi P., Sindhu V., Karthik Sambath, Arun Reddy Ravula, Geetha Palani, Sivakumar Vijayaraghavalu, Shanmuga Sundari I. and Venkatesan Perumal 8.1 Introduction 8.1.1 Cancer 8.1.2 Pancreatic cancer 8.1.3 Types of pancreatic cancer 8.2 Polymeric nanoparticles 8.2.1 Passive targeting 8.2.2 Active targeting 8.2.3 Responsive polymeric nanoparticles 8.2.4 pH-responsive polymeric nanoparticles 8.2.5 Synthesis of polymeric nanoparticles 8.2.6 Characterization of polymeric nanoparticles 8.3 Diagnosis 8.3.1 Risk factors 8.3.2 Detection of protein-based biomarkers in blood 8.3.3 Detection of nucleic-based biomarkers in blood 8.3.4 Imaging techniques 8.3.5 Electrochemical detection 8.4 Surgical management 8.4.1 Preoperative biliary drainage 8.4.2 Anastomotic technique 8.4.3 Minimally invasive surgery 8.4.4 Vascular resection 8.5 Medical management 8.5.1 Chemotherapy 8.5.2 Immunotherapy 8.5.3 Radiotherapy 8.5.4 Targeted therapy 8.5.5 Antibody-mediated therapy 8.5.6 Synergistic therapy 8.5.7 Radiodynamic therapy 8.6 Conclusion References 9. Metallic nanoparticles-based drug delivery for pancreatic cancer Sara Natalia Moya Betancourt, Jorge Gustavo Uranga, Viviana Beatriz Daboin, Paula Gabriela Bercoff and Julieta Soledad Riva 9.1 Introduction 9.2 Gold nanoparticles 9.3 Silver nanoparticles 9.4 Iron oxide nanoparticles 9.5 Other metallic nanoparticles (Pd, Pt, CuO, ZnO, TiO2) 9.6 Mesoporous silica nanoparticles 9.7 Conclusion Acknowledgments Conflicts of interest References 10. Empowering treatment strategies for pancreatic cancer by employing lipid nanoparticle-driven drug delivery Sumit Sheoran, Swati Arora, Aayushi Velingkar, Smita C. Pawar and Sugunakar Vuree 10.1 Introduction 10.2 Symptoms and risk factors of pancreatic cancer 10.2.1 The stages of pancreatic cancer? 10.3 Lipid nanoparticles 10.4 Solid lipid nanoparticles 10.5 Limitations of solid lipid nanoparticles and way to overcome 10.6 High pressure-induced drug degradation 10.7 Lipid crystallization and drug incorporation 10.8 Several colloidal species coexist 10.9 Nanostructured carriers of lipid (solid lipid nanoparticles and nanostructured lipid carriers) 10.9.1 Solid lipid nanoparticles and nanostructured lipid carriers for drug delivery 10.9.2 Solid lipid nanoparticles as delivery carriers for anticancer agents 10.9.3 Routes of delivering 10.10 Applications of solid lipid nanoparticles in pancreatic cancer 10.11 Conclusion References 11. Solid lipid nanoparticle-based drug delivery for pancreatic cancer Dipanjan Ghosh, Gouranga Dutta, Arindam Chatterjee, Abimanyu Sugumaran, Gopal Chakrabarti and Sivakumar Manickam 11.1 Introduction 11.2 Lipid classifications for solidlipid nanoparticle synthesis 11.3 Preparations techniques of solid lipid-based nanoparticles 11.3.1 High-pressure homogenization 11.3.2 Ultrasonication 11.3.3 Coacervation 11.3.4 Solvent emulsification evaporation 11.3.5 Microemulsions 11.4 Role of pancreatic lipase and lipid nanoparticle in pancreatic cancer therapy 11.5 Enhancing cancer therapeutic efficacy with lipid-based nanoparticles 11.5.1 Gemcitabine 11.5.2 Paclitaxel 11.5.3 Irinotecan 11.5.4 Capecitabine 11.5.5 5-fluorouracil 11.5.6 RNA-based delivery system 11.6 Future aspects References 12. Dendrimers and carbon nanotubes-based drug delivery for pancreatic cancer Mehmethan Yildirim, Durmus Burak Demirkaya and Serap Yalcin 12.1 A brief overview of pancreatic cancer 12.2 Drug delivery for cancer therapy 12.3 Carbon nanotubes 12.4 Dendrimers 12.4.1 Poly-L-lysine-based dendrimers 12.4.2 Polyamidoamine dendrimers 12.4.3 Polypropylene imine dendrimers 12.4.4 Frechet-type dendrimers 12.4.5 Core-shell tecto dendrimer 12.4.6 Chiral dendrimers 12.4.7 Liquid crystal dendrimers 12.4.8 Peptide dendrimers 12.4.9 Polyester dendrimers 12.5 Dendrimers and carbon nanotubes-based drug delivery for pancreatic cancer 12.6 Conclusion References Further reading Part C Recent advances and future prospective for pancreatic cancer 13. Personalized medicine and new therapeutic approach in the treatment of pancreatic cancer Hanieh Azari, Ghazaleh Khalili-Tanha, Elham Nazari, Mina Maftooh, Seyed Mahdi Hassanian, Gordon A. Ferns, Majid Khazaei and Amir Avan 13.1 Introduction 13.1.1 Pancreatic cancer: common treatment 13.2 Could personalized medicine transform healthcare? 13.2.1 What is personalized medicine? 13.2.2 Precision or personalized medicine: what's the difference? 13.2.3 Advantages of personalized medicine 13.3 The role of personalized medicine in pancreatic cancer 13.4 Recent progress in personalized medicine for pancreatic cancer therapy 13.5 The molecular landscape of pancreatic cancer 13.6 Genomic subgroups 13.7 Transcriptomic subgroup 13.8 Predictive markers of pancreatic cancer for personalized therapy 13.9 Examples of precision medicine in pancreatic cancer 13.9.1 Patient derived xenograft 13.9.2 Patient's derived organoid 13.10 The advantages of microfluidic devices 13.11 General scheme of producing a pancreatic organoid 13.12 Some applications of pancreatic organoids 13.12.1 RNA-based therapeutic tool for personalized PDAC treatment 13.12.2 Radiomics and deep learning in personalized medicine 13.13 The quantitative imaging methods for pancreatic cancer diagnosis, prognosis, and prediction 13.14 Challenges and innovations in personalized medicine care 13.15 Challenges in the treatment of pancreatic cancer 13.16 The challenges from an oncologist's perspective 13.17 Opportunities for personalized therapy in the near future 13.18 Conclusion Declarations of interest References 14. Clinical practice guidelines for interventional treatment of pancreatic cancer Ghazaleh Pourali, Ghazaleh Donyadideh, Shima Mehrabadi, Mina Maftooh, Seyed Mahdi Hassanian, Gordon A. Ferns, Majid Khazaei and Amir Avan 14.1 The definition of pancreatic cancer and its classification in clinic 14.2 Incidence and epidemiology and risk factors 14.2.1 Modifiable risk factors 14.2.2 Nonmodifiable risk factors 14.3 Surgical treatment of pancreatic cancer 14.4 Nonsurgical therapies 14.4.1 Chemotherapy 14.4.2 Chemoradiotherapy 14.4.3 Radiotherapy 14.4.4 Ablative techniques 14.5 Treatment in metastatic patient 14.5.1 First-line chemotherapy 14.5.2 Second-line chemotherapy 14.5.3 Side effects and future perspective Grant Conflict of interest References 15. Aptamer-mediated nano-therapy for pancreatic cancer Seyyed Mobin Rahimnia, Sadegh Dehghani, Majid Saeedi, Amin Shad and Rezvan Yazdian-Robati 15.1 Introduction 15.2 Nanotechnology as a novel cancer therapeutic strategy 15.3 Aptamers as an advance targeted strategy in cancer diagnosis and treatment 15.4 Aptamer design approaches 15.5 Methods for coupling aptamers to nanoparticles 15.6 Tumor markers for pancreatic cancer 15.7 Aptamers against pancreatic cancer 15.8 Aptamers in clinical trials for pancreatic cancer 15.9 Aptamer-functionalized nanocarriers against pancreatic cancer 15.9.1 Aptamer-functionalized calcium phosphosilicate nanoparticles 15.9.2 Aptamer-functionalized gold nanoparticles 15.9.3 Aptamer-functionalized lipid nanoparticles 15.9.4 Aptamer-functionalized magnetic nanoparticles for treatment of pancreatic cancer 15.9.5 Aptamer-functionalized polymeric nanoparticles 15.9.6 Aptamer-functionalized albumin nanoparticles 15.10 Conclusion Conflict of interest References 16. Photodynamic therapy for pancreatic cancer Rezvan Yazdian-Robati, Atena Mansouri, Peyman Asadi, Mehdi Mogharabi-Manzari and Mohsen Chamanara 16.1 Pancreatic cancer 16.2 Principles of photodynamic therapy 16.3 Elements of photodynamic therapy 16.3.1 Photosensitizers agents in photodynamic therapy 16.3.2 Light (600800 nm) 16.3.3 Oxygen 16.4 Nanoparticles mediated photodynamic therapy for pancreatic cancer 16.5 Combination of photodynamic therapy with other therapies in pancreatic cancer treatment 16.5.1 Combination of photodynamic therapy with radiation therapy 16.5.2 Combination of photodynamic therapy with immunotherapy 16.5.3 Combination of photodynamic therapy with chemotherapy 16.5.4 Combination of photodynamic therapy with chemotherapy and immunotherapy 16.5.5 Combination of photodynamic therapy with sonodynamic therapy 16.5.6 Combination of photodynamic therapy with photothermal therapy 16.6 Summary and outlook Declaration of competing interest References 17. Future prospect of nano-based drug delivery approaches against pancreatic cancer and expected pitfalls of the technology K.R. Manu, Gurleen Kaur, Ananya Kar, Lopamudra Giri, Waleed H. Almalki, Neelima Gupta, Amirhossein Sahebkar, Prashant Kesharwani and Rambabu Dandela 17.1 Introduction 17.2 Conventional therapy for pancreatic cancer 17.2.1 Surgery 17.2.2 Chemotherapy 17.2.3 Radiation therapy 17.2.4 Targeted therapy 17.3 The prospects of nanotechnology in pancreatic cancer treatment 17.4 Applications of various types of nano-based drug delivery systems for pancreatic cancer therapy 17.4.1 Hydrogel-based drug delivery systems 17.4.2 Nanoemulsion-based drug delivery systems 17.4.3 Liposome- and niosome-based drug delivery systems 17.4.4 Polymeric nanoparticlebased drug delivery systems 17.4.5 Micelle-based drug delivery systems 17.4.6 Metallic nanoparticlebased drug delivery systems 17.4.7 Solid lipid nanoparticlebased drug delivery systems 17.4.8 Quantum dotbased drug delivery systems 17.4.9 Dendrimer-based drug delivery systems 17.4.10 Carbon nanotubebased drug delivery systems 17.5 Challenges of nano-based drug delivery system for pancreatic cancer therapy 17.6 Conclusion and future perspective Acknowledgments Reference Index
