Biomaterials for Cancer Therapeutics,
Edition 2 Evolution and Innovation
Edited by Kinam Park

Publication Date: 04 Mar 2020

Biomaterials for Cancer Therapeutics: Evolution and Innovation, Second Edition, discusses the role and potential of biomaterials in treating this prevalent disease. The first part of the book discusses the fundamentals of biomaterials for cancer therapeutics. Part Two discusses synthetic vaccines, proteins and polymers for cancer therapeutics. Part Three focuses on theranosis and drug delivery systems, while the final set of chapters look at biomaterial therapies and cancer cell interaction.

Cancer affects people of all ages, and approximately one in three people are estimated to be diagnosed with cancer during their lifetime. Extensive research is being undertaken by many different institutions to explore potential new therapeutics, and biomaterials technology is being developed to target, treat and prevent cancer. Hence, this book is a welcomed resource to the discussion.

Key Features

  • Provides a complete overview of the latest research into the potential of biomaterials for the diagnosis, treatment and prevention of cancer
  • Discusses how the properties of specific biomaterials make them important in cancer treatment
  • Covers synthetic vaccines, proteins and polymers for cancer therapeutics
About the author
Edited by Kinam Park, Professor of Biomedical Engineering and Professor of Pharmaceutics, Purdue University, USA
Table of Contents
  1. Cancer: so common and so difficult to deal with
  2. 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


  3. Phenotypic evolution of cancer cells: structural requirements for survival
  4. 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


  5. Immunoactive drug carriers in cancer therapy
  6. 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



  7. Treating cancer by delivering drug nanocrystals
  8. 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


  9. Polymer therapeutics
  10. 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



  11. 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


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

    1. Summary


  1. Biomaterials for gene editing therapeutics
  2. 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



  3. 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


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


  1. 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


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



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




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



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



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


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


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


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



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



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


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


Book details
ISBN: 9780081029831
Page Count: 782
Retail Price : £245.00

9780081001479; 9780857096999; 9780323390804

Biomaterials scientist and engineers; Biomedical engineers; Biomedical and pharmaceutical scientists