Biomaterials for Cancer Therapeutics

Biomaterials for Cancer Therapeutics

Evolution and Innovation

2nd Edition - March 4, 2020

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  • Editor: Kinam Park
  • eBook ISBN: 9780081029848
  • Paperback ISBN: 9780081029831

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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


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

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 α-Tocopherol succinate

           3.6.2 D-α-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



Product details

  • No. of pages: 782
  • Language: English
  • Copyright: © Woodhead Publishing 2020
  • Published: March 4, 2020
  • Imprint: Woodhead Publishing
  • eBook ISBN: 9780081029848
  • Paperback ISBN: 9780081029831

About the Editor

Kinam Park

Kinam Park is Showalter Distinguished Professor of Biomedical Engineering & Professor of Pharmaceutics at Purdue University, USA. His research focuses in the areas of nano/micro particles, polymer micelles, drug-eluting stents, extracellular matrix, fast dissolving tablets, and smart hydrogels.

Affiliations and Expertise

Professor of Biomedical Engineering and Professor of Pharmaceutics, Purdue University, USA

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