- Cancer: so common and so difficult to deal with
Ana Santos Cravo and Randall Mrsny
1.1 Introduction
1.2 General classification of cancers
1.3 Early detection—still the best medicine
1.4 Cancer genetics and epigenetics
1.5 Factors that make a cell cancerous
1.6 The concept of a transition from chronic inflammation to cancer
1.7 Current methods to treat various cancers
1.8 Cancer as a real estate concept—location, location, location
1.9 Areas of greatest unmet need in treating cancers
1.10 Conclusion and future trends
References
- Phenotypic evolution of cancer cells: structural requirements for survival
Farzaneh Atrian and Sophie A. Lelie `vre
2.1 Introduction
2.1.1 Phenotypic overview of cancer progression
2.1.2 Evolution of the organization of nuclei in cancer cells
2.1.3 Involvement of nuclear structural proteins in gene transcription
2.1.4 The extracellular matrix component of the tumor microenvironment
2.1.5 Drug resistance in cancer
2.2 Mechanical properties of the tumor microenvironment
2.2.1 Matrix remodeling in cancerous tissue
2.2.2 Influence of matrix stiffness and tissue geometry on cancer phenotype
2.2.3 Future directions: design of "intelligent" biomaterials that respond to microenvironmental changes
2.3 Nuclear structure as a mediator of information
2.3.1 Physical properties of the cell nucleus
2.3.2 Nuclear proteins involved in mechanosensing
2.3.3 Future directions: identification of internal nuclear features that have the ability to link microenvironmental changes and chromatin
2.4 Nuclear dynamics in anticancer drug resistance and cell survival
2.4.1 Drug resistance and survival in cancer cell populations
2.4.2 Nuclear dynamics and alterations in genome functions
2.4.3 Future directions: platforms and biomaterials to integrate nuclear reorganization and cell survival in tumors
2.5 Conclusion
References
- Immunoactive drug carriers in cancer therapy
Fanfei Meng, Soonbum Kwon, Jianping Wang and Yoon Yeo
3.1 Introduction
3.2 Synthetic polymers
3.2.1 Polyethyleneimine
3.2.2 Pluronic polymers
3.2.3 Polymeric drugs
3.3 Polysaccharides
3.3.1 Chitosan
3.3.2 Hyaluronic acid
3.3.3 Chondroitin sulfate
3.3.4 Alginate
3.3.5 Pectin
3.4 Polypeptides
3.4.1 Polypeptides as drug and gene carriers
3.4.2 Antiproliferative or immune adjuvant activities of polypeptides
3.5 Polar lipids
3.5.1 Polar lipids in drug and gene delivery
3.5.2 Anticancer activities of polar lipids
3.5.3 Immune activities of polar lipids
3.6 Vitamin E derivatives
3.6.1 a-Tocopherol succinate
3.6.2 D-a-Tocopheryl polyethylene glycol 1000 succinate
3.7 Inorganic materials
3.7.1 Iron oxide
3.7.2 Graphene oxide
3.7.3 Others: Au, SiO2, and TiO2
3.8 Conclusion
Acknowledgment
References
- Treating cancer by delivering drug nanocrystals
Wei Gao, Clairissa D. Corpstein and Tonglei Li
4.1 Introduction
4.2 Preparation of drug nanocrystals
4.2.1 Top-down approach
4.2.2 Top-down approach
4.3 Cellular interaction and intracellular delivery
4.3.1 Cellular update and hybrid nanocrystal
4.3.2 Hybrid nanocrystal with environment-sensitive fluorophore
4.4 In vivo performance
4.5 Conclusion
References
- Polymer therapeutics
Kyung Hyun Min, Hong Jae Lee and Sang Cheon Lee
5.1 Introduction
5.2 Polymeric drugs for multivalent biorecognition
5.2.1 Polymer therapeutics for cross-linking of antigens on the cell surface
5.2.2 Polymeric drugs conjugated with an apoptosis-inducing ligand’
5.3 Polymeric drugs inhibiting chemokine receptors
5.4 Polymeric P-glycoprotein inhibitors
5.4.1 Multidrug resistance by P-glycoprotein
5.4.2 Classes of polymeric P-glycoprotein inhibitors
5.5 Summary and future perspectives
Acknowledgment
References
- pH-sensitive biomaterials for cancer therapy and diagnosis 000
Kyoung Sub Kim, Jun Hu and You Han Bae
6.1 Introduction
6.2 Nature of pH-sensitivity
6.2.1 Protonation/deprotonation
6.2.2 Acid-labile bonds
6.3 Tumor pH probe
6.4 Nanosystem activation by pH
6.4.1 Simultaneous activation by extracellular/subcellular pH by design
6.4.2 Sequential activation by tumor extracellular/subcellular pH
6.5 Applications of pH-sensitive biomaterials
6.5.1 Drug delivery
6.5.2 Tumor imaging
6.6 Conclusion and perspective
References
7. Nucleic acid anticancer agents
S. Samaddar and D.H. Thompson
7.1 Introduction
7.2 Oligonucleotides targeting RNA
7.2.1 siRNA (short interfering RNA)
7.2.2 Short hairpin RNA
7.2.3 microRNA
7.2.4 Splice-switching oligonucleotides
7.2.5 Gapmer
7.2.6 DNAzyme
7.3 Oligonucleotides targeting DNA
7.3.1 Triplex folding oligonucleotides
7.4 Oligonucleotides targeting proteins
7.4.1 Oligonucleotides that stimulate the immune system
7.4.2 Aptamers
7.4.3 DNA decoys
7.5 Chemical modifications of nucleic acids to boost their in vivo efficacy
7.5.1 Carbohydrate modifications
7.5.2 Backbone modification
- Summary
References
- Biomaterials for gene editing therapeutics
Gayong Shim, Dongyoon Kim, Quoc-Viet Le, Junho Byun, Jinwon Park and Yu-Kyoung Oh
8.1 Introduction
8.2 Gene editing platform
8.2.1 Zinc finger nuclease
8.2.2 Transcription activatorlike effector nuclease
8.2.3 Clustered regularly interspaced short palindromic repeatassociated nuclease Cas9
8.2.4 Others
8.3 Delivery strategies for gene editing
8.3.1 Delivery vectors
8.3.2 Barriers for intracellular delivery
8.3.3 Mode of gene editing
8.4 Biomaterial-based delivery of gene editing systems
8.4.1 Polymers
8.4.2 Lipids
8.4.3 Peptides
8.4.4 Inorganic materials
8.4.5 Nucleic acidbased nanostructures
8.5 Clinical trials
8.6 Challenges and future perspectives
Acknowledgments
References
- Liquid biopsies for early cancer detection
Stefan H. Bossmann
9.1 Introduction
9.2 Liquid biopsies
9.2.1 Liquid biopsies based on circulating tumor cells
9.2.2 Liquid biopsies based on the human genome and characteristic mutations in cancer
9.3 Technologies for liquid biopsies based on genetic and epigenetic mutations
9.3.1 State-of-the-art in liquid biopsies
9.4 Exosomes
9.5 Cytokines and other signaling proteins as biomarkers for cancer progression
9.6 Classic methods of cytokine detection in biospecimens
9.6.1 Enzyme-linked immunosorbant assay
9.6.2 Radioimmunoassays
9.6.3 Chemiluminescence assays
9.6.4 Cytokine bioassays
9.6.5 Multiparametric flow cytometry in conjunction with using (magnetic) beads
9.6.6 Enzyme-linked immunospots (ELISPOT and FLUOROSPOT)
9.6.7 Bar code technology
9.6.8 Cytokine detection by means of surface-enhanced Raman spectroscopy
9.7 Protease and kinase networks
9.7.1 Protease activity and cancer
9.8 Outlook: cost-effectiveness will be an important factor
References
10. Nanotechnology for cancer screening and diagnosis: from innovations to clinical applications R. Zeineldin
10.1 Introduction
10.1.1 Biosensing and screening of biomarkers
10.1.2 Imaging
10.2 Nanotechnology for cancer diagnosis
10.2.1 Properties and advantages of nanoparticles and nanomaterials
10.3 Nanotechnology-based biosensing platforms
10.3.1 Lab-on-a-chip and microarrays
10.3.2 Sphere-based platforms
10.3.3 Magnetic-based assays
10.3.4 Other platforms
10.4 Nanotechnology for biosensing—early detection of cancer
10.4.1 Screening—enhancing biomarkers detection
10.4.2 Detecting circulating tumor cells
10.4.3 Clinical applications of nanotechnology in biosensing
10.5 Nanotechnology for cancer imaging
10.5.1 Targeted molecular imaging
10.5.2 Types of imaging enabled by nanomaterials
10.5.3 Types of imaging enhanced by nanomaterials
10.5.4 Nano-based multimodal imaging
10.5.5 Theranostics
10.5.6 Nanotechnology for tumor classification/staging
10.5.7 Concerns with using nanomaterials in imaging
10.5.8 Clinical applications for nanotechnology in cancer imaging
10.6 Conclusion and future trends
References
- Advances and clinical challenges in biomaterials for in vivo tumor imaging
Andre ´ O’Reilly Beringhs, Raana Kashfi Sadabad and Xiuling Lu
11.1 Current state of tumor imaging in the clinic
11.1.1 Positron emission tomography
11.1.2 Magnetic resonance imaging
11.1.3 X-ray computed tomography
11.2 Potential clinical uses of novel biomaterials for tumor imaging
11.3 Preclinical advances in biomaterials for tumor imaging
11.3.1 Quantum dots
11.3.2 Carbon-based materials
11.3.3 Lipid-based materials
11.3.4 Polymer-based materials
11.4 Riskbenefit assessment and perspectives
References
12. Macroscopic fluorescence lifetime-based Fo ¨rster resonance energy transfer imaging for quantitative ligandreceptor binding
Alena Rudkouskaya, Denzel E. Faulkner, Nattawut Sinsuebphon, Xavier Intes and Margarida Barroso
12.1 Assessment of target engagement in drug delivery
12.2 Challenges in the quantification of target engagement in preclinical cancer research
12.2.1 Enhanced permeability and retention effect
12.2.2 Biochemical and imaging methods to assess target engagement
12.2.3 Fo ¨rster resonance energy transfer to quantify target engagement
12.3 In vivo molecular imaging in preclinical research
12.3.1 Positron emission tomography versus optical imaging
12.3.2 Visible and near-infrared fluorescence lifetime imaging
12.3.3 Preclinical applications of fluorescence lifetime imaging Fo ¨rster resonance energy transfer imaging
12.4 Fluorescence lifetime imaging Fo ¨rster resonance energy transfer imaging to quantify ligandreceptor binding
12.4.1 Transferrintransferrin receptor-mediated drug delivery
12.4.2 Wide-field time-resolved macroscopy fluorescence lifetime imaging optical imager
12.4.3 MFLI Fo ¨rster resonance energy transfer imaging of transferrintransferrin receptor binding
12.4.4 Advantages and limitations of MFLI Fo ¨rster resonance energy transfer imaging
12.5 Imaging with high-resolution beyond the microscopy limit: mesoscopic fluorescence molecular tomography of thick tissues
12.6 Future directions of MFLI Fo ¨rster resonance energy transfer imaging in the clinic
Acknowledgments
References
Further reading
13. Suppression of cancer stem cells
Carla Garcia-Mazas, Sheila Barrios-Esteban, Noemi Csaba and Marcos Garcia-Fuentes
13.1 Introduction
13.1.1 Models of cancer origin
13.1.2 Characteristics of cancer stem cells
13.1.3 The cancer stem cell niche
13.1.4 Cancer stem cell drug resistance
13.2 Pharmacological strategies for suppressing cancer stem cells
13.2.1 Druggable pharmacological strategies
13.2.2 Gene therapies for cancer stem cells
13.3 Nanomedicines for cancer stem cell therapy
13.3.1 Delivery of small drugs to cancer stem cells
13.3.2 Gene delivery to cancer stem cells
13.3.3 Targeting to cancer stem cells
13.4 Concluding remarks
Acknowledgments
Abbreviations
References
14. Comparison of two- and three-dimensional cancer models for assessing potential cancer therapeutics
Bailu Xie, Nicole Teusch and Randall Mrsny
14.1 Introduction
14.2 A brief history of two- and three-dimensional in vitro cancer models
14.3 Methods used for high-throughput testing of potential chemotherapeutics in vitro
14.4 Practical aspects of techniques to establish three-dimensional in vitro cancer models
14.4.1 Spinner flasks/bioreactors
14.4.2 Gel-like substances/scaffold structures (hydrogels)
14.4.3 The hanging drop format
14.4.4 Low-attachment plates with centrifugation
14.4.5 Magnetic levitation
14.4.6 Micropatterning
14.4.7 Microencapsulation
14.4.8 Microfluidics
14.4.9 Bioprinting
14.5 The future of three-dimensional cancer models
Acknowledgments
References
15. Engineered tumor models for cancer biology and treatment
Hye-ran Moon and Bumsoo Han
15.1 Introduction
15.2 Complexities of cancers and the tumor microenvironment
15.3 Design and development of tumor models
15.3.1 Spheroids and organoids
15.3.2 Animal models
15.3.3 Microfluidic models
15.4 Challenges and opportunities
Acknowledgments
References
16. Cancer mechanobiology: interaction of biomaterials with cancer cells
Sarah Libring and Luis Solorio
16.1 What is mechanotransduction?
16.2 Native mechanobiology through cancer’s progression
16.2.1 The primary tumor microenvironment
16.2.2 The premetastatic niche and primary cell motility
16.2.3 Secondary tumor sites: dormancy, reactivation, and drug resistance
16.3 Researching mechanotransduction
16.3.1 Techniques for studying mechanotransduction
16.3.2 Cancer models
16.3.3 Material selection
16.4 Conclusion and future trends
References
17. Immunostimulatory materials
Evan Scott and Sean Allen
17.1 Introduction
17.2 Immunostimulation
17.2.1 General mechanisms of immunostimulation: antigen-presenting cells and Toll-like receptors
17.2.2 Cellular mediators of immune dysregulation within the tumor microenvironment
17.3 Immunostimulatory hydrogels
17.3.1 Sustained delivery of immunomodulators
17.3.2 Hydrogels as artificial sites of immune stimulation
17.4 Enhancing immunostimulation via nanobiomaterials
17.4.1 Designing nanoscale biomaterials for cellular targeting
17.4.2 Biodistributions of administered nanobiomaterials
17.4.3 Antigen-presenting cells as key targets of therapeutic immunostimulation
17.4.4 Nanobiomaterials for RNA interfering-based cancer therapy
17.4.5 Nanobiomaterials to enhance cancer vaccination
17.4.6 Nanobiomaterials to enhance adoptive T-cell therapy
17.4.7 Future directions of nanobiomaterials for cancer immune dysregulation
References
18. Biomaterials for cancer immunotherapy
Kinan Alhallak, Jennifer Sun, Barbara Muz and Abdel Kareem Azab
18.1 Noncellular immunotherapies
18.1.1 Delivery of antibodies
18.1.2 Delivery of immunomodulators
18.1.3 Delivery of other molecules
18.2 Artificial cellular immunotherapies
18.2.1 Artificial antigen-presenting cells
18.2.2 Artificial T cells
18.3 Adoptive cell therapy
18.3.1 T cells
18.3.2 Natural killer cells
18.3.3 Macrophages
18.3.4 Dendritic cells
18.4 Gene-based immunotherapies
18.4.1 Small interfering RNA
18.4.2 Messenger RNA
18.5 Conclusion
References
19. Lymph node targeting for improved potency of cancer vaccine
Guangsheng Du and Xun Sun
19.1 Introduction
19.2 Tumor-draining lymph node as a target for cancer vaccines
19.2.1 The role of lymphatic vessels and lymph node in vaccination
19.2.2 Lymphatic system in cancer conditions
19.3 Targeting strategies for lymph nodes
19.3.1 Direct intranodal injection
19.3.2 Passive draining of nanoparticulate vaccines from the interstitial space
19.3.3 Active binding with lymphatic endothelium by ligandreceptor interaction
19.3.4 Albumin "hitchhiking" approach
19.4 The dilemma between lymph node targeting and uptake and retention in antigen-presenting cells
19.5 Lymph nodetargeted vaccine carriers for cancer therapy
19.5.1 Polymeric micelles
19.5.2 Lipid-coated inorganic nanoparticles
19.5.3 Polymeric nanoparticles
19.5.4 Liposomes
19.5.5 Other nanoparticles
19.6 Summary, prospection, and conclusion
Acknowledgments
References
20. Immunogenic clearance-mediated cancer vaccination
Gi-Hoon Nam, Yoosoo Yang and In-San Kim
20.1 Introduction
20.2 Current cancer immunotherapies using cancer vaccines
20.2.1 Conventional cancer vaccines: past and present
20.2.2 Limitations and challenges of conventional cancer vaccines
20.3 Immunogenic clearance
20.3.1 Immunogenic cell death for releasing neoantigens and danger-associated molecular patterns
20.3.2 Enhancing tumor cell phagocytosis by innate immune cells
20.3.3 Combination therapy utilizing immunogenic clearance
20.3.4 Biomaterials for immunogenic clearance
20.4 Enhancing the response rate of immune checkpoint blockades to tumors
20.5 Conclusion
Acknowledgments
References
21. The future of drug delivery in cancer treatment
Amit Singh and Mansoor Amiji
21.1 Introduction
21.2 Challenges with designing and personalizing cancer therapy
21.2.1 Tumor heterogeneity and complexity
21.2.2 Multidrug resistance
21.2.3 Biological barriers
21.2.4 Physiological barriers
21.3 Challenges with nanotechnology-based drug delivery
21.3.1 Drug encapsulation and stability
21.3.2 Tumor-specific delivery and targeting
21.3.3 Pharmacokinetic modulation
21.3.4 Intracellular and subcellular delivery
21.4 Safety challenges with nano-drug delivery
21.4.1 Material safety issues
21.4.2 Limitations of characterization tools and biological models
21.4.3 Immunological profiling and immunotoxicity
21.5 Formulation challenges with nano-drug delivery
21.5.1 Nanoparticle design
21.5.2 Analytical characterization
21.5.3 Manufacturing and scale-up issues
21.6 Current clinical landscape in nano-based drug delivery in cancer
21.6.1 Lipid nanoparticles
21.6.2 Polymeric nanoparticles
21.6.3 Protein nanoparticles
21.7 Conclusion and future perspective
References
22. Development of clinically effective formulations for anticancer applications: why it is so difficult?
David Needham
22.1 "Executive" overview
22.2 Introduction
22.2.1 So, you want to develop a clinically effective formulation?
22.2.2 My motivation and goal
Part A. The nonscientific part
22.3 It is actually not that difficult to get drugs approved (there are lots of them)
22.4 What about cancer statistics and cancer trials?
22.5 This regulated process costs money to cross "the valley of death"
22.6 But just because it is approved does not mean it works
22.7 And there are people who want to make money and are making money (which is fine)
Part B. The scientific part
22.8 For cancer though, yes, it is difficult (but I think it is not impossible)
22.9 The intravenous dosing problem for cancer: from here to there
22.10 What is nanomedicine? And why?
22.11 The only way to get a chemotherapeutic drug throughout a whole tumor is to release it in the blood stream of the tumor
22.12 "Make the drug look like the cancer’s food": our efforts to treat osteosarcoma
22.13 Final thoughts
References
