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- Herausgeber: John Wiley & Sons
- Kategorie: Wissenschaft und neue Technologien
- Serie: Advances in Nanotechnology and Applications
- Sprache: Englisch
NANOPARTICLES FOR THERAPEUTIC APPLICATIONS The main goal of this book is to provide information on theranostic applications of various nanomaterials for different diseases with self-explanatory illustrations and fundamental descriptions of a plethora of properties of molecular traits. The author has written a fascinating book on research topics and fundamentals in the cross-disciplinary area of nanotechnology and bioscience in which she successfully fuses otherwise divergent research topics of this rapidly emerging area. The book deals with the use of nanomaterials for combatting various diseases and disorders of the human body. The three chapters of the first part of this book deal with the areas in which nanotechnology has contributed to nanomedicine. In the second part, different disorders like cancer, neurodegenerative diseases, genetic diseases, infectious diseases, cardiovascular disorders, eye, dentistry, bone, and cartilage-affecting diseases are discussed. In the chapters related to a disease or disorder of a particular organ, a basic brief introduction to them is given as well. Audience The book will be read by researchers, scientists, and graduate students in biotechnology, nanotechnology, materials science, and nanomedicine/biomedicine.
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Veröffentlichungsjahr: 2022
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Table of Contents
Cover
Title Page
Copyright
Dedication
Foreword
Preface
Part I: NANO-FLOTILLAS TRAVERSING IN THE VEIN AS CARRIERS TO DELIVER THERANOSTICS
1 Diagnostic and Therapeutic Systems Using Nanomaterials
1.1 Introduction
1.2 Nanodiagnostic Agents
1.3 Summary
References
2 Nano Trojan Horses for Delivery of Peptides and Protein Drugs
2.1 Introduction
2.2 Peptides
2.3 Role of Nanoparticles in Peptide Drug Delivery
2.4 Protein
2.5 Role of Nanoparticles (NPs) in Protein Drug Delivery
2.6 Summary
References
3 Biomimetic Nanomaterials as Smart Scaffolds for Tissue Regeneration
3.1 Introduction
3.2 Scaffold
3.3 Biomaterials for the Fabrication of Scaffold
3.4 Nanomaterials for Versatile Scaffolds
3.5 Application of Scaffold for Various Tissue Regeneration and Incorporation of Nanomaterials
3.6 Considerations for Manufacturing a Scaffold at Commercial Level
3.7 Conclusion
References
Part II: THE CARDINAL ROLE OF BIOMEDICAL NANOTECHNOLOGY
4 Nanodiagnostics and Nanotherapeutics: A Powerful Tool for Ablation of Cancer
4.1 Introduction
4.2 Molecular Diagnostics
4.3 Radiological Diagnostics for Cancer
4.4 Biopsy
4.5 Nanodiagnostics for Cancer
4.6 Summary
References
5 Genetic Diseases and Nanotechnology-Based Theranostics
5.1 Introduction
5.2 Nanotechnologies and Microchips in Genetic Diseases
5.3 Nanotechnology and Gene Therapy for Genetic Disease
5.4 Gene Silencing Therapy
5.5 Ribonucleic Acid (RNA) Therapy and Nanotechnology
5.6 Nanoparticles-Based Therapies for Various Chromosomal Disorders
5.7 Summary
References
6 The Role of Biomedical Nanotechnology in CNS and Neurological Disorders
6.1 Introduction
6.2 Parkinson’s Disease
6.3 Alzheimer’s Disease
6.4 Epilepsy/Seizure Disorder
6.5 Schizophrenia
6.6 Summary
References
7 Nanotechnology-Based Theranostics for Fighting Infectious Diseases
7.1 Introduction
7.2 Diseases Caused by Prions
7.3 Diseases Caused by Virus
7.4 Diseases Caused by Bacteria
7.5 Diseases Caused by Fungi
7.6 Diseases Caused by Parasitic Protozoa
7.7 Diseases Caused by Helminths
7.8 Summary
References
8 Nanotheranostics for Cardiovascular Diseases
8.1 Introduction
8.2 Nanotheranostics for Cardiovascular Diseases
8.3 Summary
References
9 Role of Nanotechnology in Combatting Disease and Disorders of Ophthalmology
9.1 Introduction
9.2 Structure and Anatomy of the Human Eye
9.3 Eye Diseases and Disorders
9.4 Blindness
9.5 Nanotherapy for Ocular Diseases and Disorders
9.6 Glaucoma: Potential Implications of Nanotechnology and Nanomedicine
9.7 Cataract: Potential Implications of Nanotechnology and Nanomedicine
9.8 Uveitis (Eye Inflammation) Therapy by Nanozyme (Superoxide Dismutase 1)
9.9 Contact Lenses for Ocular Theranostic
9.10 Nanodiagnostic for Ocular Diseases and Disorders
9.11 Summary and Future Perspective
References
10 Use of Nanotechnology in Dentistry
10.1 Introduction
10.2 Diseases and Disorders of Teeth
10.3 Nanotheranostics Used in Dentistry
10.4 Conclusion
References
Index
Also of Interest
End User License Agreement
List of Illustrations
Chapter 1
Figure 1.1 Barcode assay of PSA using nanoparticles. A schematic representation ...
Figure 1.2 A cantilever beam.
Figure 1.3 Cantilever beam response: (a) initial state and (b) sensing state.
Figure 1.4 Transmission electron microscopy image of carbon dot.
Figure 1.5 A schematic diagram showing functionalization of CNT (having both end...
Figure 1.6 (A) Dangling orbital shown by vertical lines present over a smooth me...
Figure 1.7 Schematic diagram of CNT-based biosensor.
Figure 1.8 Schematic of a CNT showing presence of dangling bonds due to electron...
Figure 1.9 Schematic diagram of (a) Traditional method of generating X-rays; (b)...
Figure 1.10 Schematic representation of use of tissue engineering on a scaffold ...
Figure 1.11 Schematic diagram of a nerve cell or neuron.
Figure 1.12 Schematic diagram of basic structural arrangement of dendrimer.
Figure 1.13 Schematic illustration of detecting DNA hybridization signal by inte...
Figure 1.14 Relation between the size of gold nanoparticles and their melting po...
Figure 1.15 Curie point.
Figure 1.16 Superparamagnetism.
Figure 1.17 SEM image of SPION.
Figure 1.18 Trapping a particle with light.
Figure 1.19 Serum albumin - C2936H4624N786O889S41, Mol. Wt. 66,500 Dalton. It ha...
Chapter 2
Figure 2.1 Schematic representation of solid phase peptide synthesis involving d...
Figure 2.2 Classification of AMPs.
Figure 2.3 Some peptide toxins: (a) Magainin from
Xenopus laevis
, (b) Melittin f...
Figure 2.4 The strategies for production of homogeneous ADCs.
Chapter 3
Figure 3.1 Four constructs required for tissue engineering.
Figure 3.2 Types of stem cells.
Figure 3.3 Conventional biological scaffold fabrication techniques: (a) Gas foam...
Figure 3.4 Rapid prototyping scaffold fabrication techniques by fused deposition...
Figure 3.5 Rapid prototyping scaffold fabrication techniques by selective laser ...
Figure 3.6 Rapid prototyping scaffold fabrication techniques by solvent-based ex...
Figure 3.7 Schematic diagram of stereolithography (SLA).
Figure 3.8 Collagen structure: (a) Amino acid residues in collagen – Glycine, Pr...
Figure 3.9 Formation of fibrin from fibrinogen with the help of thrombin and Fac...
Figure 3.10 SEM of silk scaffold magnified 1500x; (Inset) Cocoon of silk worm sh...
Figure 3.11 Aggrecan a cartilaginous proteoglycan having 2318 amino acids. (Sour...
Figure 3.12 Molecular structure of chitosan.
Figure 3.13 Molecular structure of sodium alginate.
Figure 3.14 Molecular structure of Poly(ethylene glycol) (PEG). (Source: Wikiped...
Figure 3.15 Molecular structure of synthetic biodegradable polymer biomaterials ...
Figure 3.16 Phase diagram for the point at which CO2 becomes supercritical and c...
Figure 3.17 (Left) Molecular structure of phospholipid; (right) Schematic struct...
Figure 3.18 Porous multilayer scaffold based on polymer and calcium phosphate fo...
Figure 3.19 Connective tissues (Tendon, Ligament and Cartilage) of musculoskelet...
Chapter 4
Figure 4.1 Schematic of radioimmunoassay (RIA).
Figure 4.2 Enzyme-linked immunosorbent assay for immunological detection.
Figure 4.3 A standard western blot setup.
Figure 4.4 Collection of immunoprecipitants using a magnet.
Figure 4.5 Immunofluorescence methods.
Figure 4.6 MRI scan of spine showing osseus metastases involving D3, D4, D%, D6,...
Figure 4.7 PET-CT scan data of the whole body showing multiple sclerotic lesions...
Figure 4.8 (Left) Protective layers of brain (skull, meninges and fluid between ...
Figure 4.9 Anatomy of breast.
Figure 4.10 Mammogram showing normal (left) and cancerous (right) breast.
Figure 4.11 Typical sites and percentage chances of colon cancer.
Figure 4.12 (a) A DNA block copolymer-based micellar drug delivery system. The r...
Figure 4.13 Albumin C
123
H
193
N
35
O
37
. (Source: Wikipedia – Available structures).
Figure 4.14 Liposome.
Figure 4.15 Molecular structure of Chitosan (left) and Dextran (right).
Figure 4.16 Schematic of skin showing positions of melanoma/melanocytes.
Figure 4.17 Different melanoma cancers (from left to right): superficial spreadi...
Figure 4.18 Anatomy of pancreas.
Figure 4.19 General SERS-based immunoassay chip design and assay scheme: (a) Sub...
Figure 4.20 Position of prostate gland.
Figure 4.21 Urinary bladder.
Chapter 5
Figure 5.1 Schematic of an iron oxide nanoparticle with multiple layers based on...
Figure 5.2 Gene silencing.
Chapter 6
Figure 6.1 Schematic of what happens in Parkinson’s disease.
Figure 6.2 Normal cell vs. Alzheimer cell. (Source: J. Penney
et al
. Modelling A...
Figure 6.3 Curcumin (mol. structure).
Figure 6.4 Anatomy of the blood-brain barrier (BBB). (Adapted from: medicalterms...
Figure 6.5 Blood-brain barrier (BBB) crossed by different nanoparticles. (Source...
Chapter 7
Figure 7.1 Overview of the nanoparticulate systems used for drug delivery.
Figure 7.2 Digital image of normal and diseased prion. (Image created by Ian Ste...
Figure 7.3 Schematic of the structure of a typical virus showing a core of nucle...
Figure 7.4 Schematic of the structure of a typical icosahedral shape of the caps...
Figure 7.5 Schematic diagram of HIV. (Source: Fred Jonathan Edzeamey & Ansah Kof...
Figure 7.6 Scanning electron microscopic images of variety of viral structures: ...
Figure 7.7 Schematic of the structure of hepatitis C virus.
Figure 7.8 Schematic of structure of dengue virus.
Figure 7.9 Schematic of structure of polio virus.
Figure 7.10 Schematic of structure of Herpes Virus. (Source: Christiane Silke He...
Figure 7.11 Anti-herpes virus drugs.
Figure 7.12 Schematic of structure of virus. (Source: Vincent Racaniello, Struct...
Figure 7.13 Schematic of COVID-causing virus. (Source: Kuldeep Dhama
et al
., Cor...
Figure 7.14 Mechanism of killing bacteria by certain nanoparticles.
Figure 7.15 Copper-based metal-organic framework nanoparticles with peroxidase-l...
Figure 7.16 Some of the parasitic protozoa.
Figure 7.17 Schematic of a smart lipid-based nanoparticle (LBNP) system as a nan...
Chapter 8
Figure 8.1 Internal view of the human heart. (Source: © 2015 John Wiley & Sons, ...
Figure 8.2 Schematic of (a) artery and (b) vein with valve. (Copyright 2010, Joh...
Figure 8.3 Schematics of capillaries. (Source: Daly Susan M., Martin J. Leahy. ‘...
Figure 8.4 Progression of atherosclerotic plaque showing narrowing of the blood ...
Chapter 9
Figure 9.1 Anatomy of eye. (Source: Colin E Willoughby
et al
. Anatomy and physio...
Figure 9.2 Schematic of normal eye (left) and eye with keratoconus (right). (Sou...
Figure 9.3 Disorders due to refractive error.
Figure 9.4 Retinal detachment.
Figure 9.5 Open- and closed-angle glaucoma. (Source: Image courtesy of Santorio ...
Chapter 10
Figure 10.1 (a) Structure and (b) Cross section of a tooth. (Source: Wikipedia.)
Figure 10.2 Four different types of human teeth.
Figure 10.3 Anatomical schematic illustration of the periodontal tissue complex ...
Figure 10.4 Schematic of various amphiphile aggregates forming different structu...
Figure 10.5 Self-assembling peptide amphiphile. (Source: Dehsorkhi
et al
. Specia...
Figure 10.6 Dental implant as a replacement for a missing tooth that is fixed in...
List of Tables
Chapter 1
Table 1.1 Some nanoparticles-based therapeutics for medical applications.
Table 1.2 Polymeric nanoparticle (NP)-based products in the pipeline.
Chapter 2
Table 2.1 Peptides and their sequences sourced from different living beings. (So...
Chapter 3
Table 3.1 Use of CNT as scaffold for various cells and TE.
Chapter 8
Table 8.1 Application of some nanoparticles in cardiac diseases.
Chapter 10
Table 10.1 Different types of nanomaterials, nanoparticles and nanoconstructs us...
Table 10.2 Compilation of commonly used and tried nanomaterials for therapeutic ...
Guide
Cover
Table of Contents
Title Page
Copyright
Dedication
Foreword
Preface
Begin Reading
Index
Also of Interest
End User License Agreement
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Scrivener Publishing
100 Cummings Center, Suite 541J
Beverly, MA 01915-6106
Advances in Nanotechnology and Applications
Series Editor: Dr. Madhuri Sharon
E-mail: [email protected]
The unique properties of nanomaterials encourage the belief that they can be applied in a wide range of fields, from medical applications to electronics, environmental sciences, information and communication, heavy industries like aerospace, refineries, automobile, consumer and sports good and the list goes on. Studies conducted by nanotechnology experts mapping the risks and opportunities of nanotechnology have revealed enormous prospects for progress in almost all the branches of science. This book series will focus on the properties and related applications of nanomaterials so as to have a clear fundamental picture as to why nanoparticles are being tried instead of traditional methods. Since nanotechnology is encompassing various fields of science, each book will focus on one topic and will detail the basics to advanced science for the benefit of all levels of researchers.
Publishers at Scrivener
Martin Scrivener ([email protected])
Phillip Carmical ([email protected])
Nanoparticles for Therapeutic Applications
Madhuri Sharon
MRC, MNIT, Jaipur, Rajasthan, India
This edition first published 2022 by John Wiley & Sons, Inc., 111 River Street, Hoboken, NJ 07030, USA and Scrivener Publishing LLC, 100 Cummings Center, Suite 541J, Beverly, MA 01915, USA
© 2022 Scrivener Publishing LLC
For more information about Scrivener publications please visit www.scrivenerpublishing.com.
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Library of Congress Cataloging-in-Publication Data
ISBN 978-1-119-76230-0
Cover image: Pixabay.Com
Cover design by Russell Richardson
Set in size of 11pt and Minion Pro by Manila Typesetting Company, Makati, Philippines
Printed in the USA
10 9 8 7 6 5 4 3 2 1
Dedicated to my husband
Prof. Maheshwar Sharon
Who left for his heavenly abode,leaving me lost, sad, weak and confused.Immemorial moments with you gave me courage to compose myself andcomplete writing this book.These are not just words; they are my silent love and acknowledgement for you to allow me to be on the path of Nanoworld.
Foreword
In an era where a detailed understanding of chemistry, biochemistry, biology, and physics was at its peak in applications of almost every domain of science, a new idea cropped up, giving rise to the new multidisciplinary field of Nanotechnology. The continuing dramatic progress in understanding the electronic, optical, and mechanical properties of an ever-increasing variety of nanostructures has led to its applications that play a fundamental role in the advancement of biology and healthcare. This book encompasses ground-breaking discoveries of promising new avenues of research that reveal the enormous potential of emerging approaches in Nanotheranostics. The author has very concisely covered the use of nanotechnology in both therapeutics and diagnostics that can be applicable to many infectious as well as metabolic and genetic diseases and disorders. I think that students, as well as researchers who are interested in this arena, will benefit a lot from this book. Moreover, even industries will find material of interest in this book.
However, I oftentimes feel that it is extremely difficult to obtain general knowledge at the forefront of the rapidly growing areas of Nanotheranostics, even though a lot of books on nanotech have already been published over the past decade. Under these circumstances, it is particularly nice to find that Professor Madhuri Sharon has brought a nicely-written book on nanotheranostics to us, where many fascinating research topics and fundamentals in the cross-disciplinary area of nanotechnology and bio-science are aptly presented and discussed. I think that the author is quite successful in “fusing” otherwise divergent research topics of this rapidly emerging area. The present book is a good introduction for undergraduate/graduate students and researchers in such interdisciplinary research fields encompassing nanotechnology, materials science, nanomedicine, and bionanotechnology.
I would like to invite readers interested in the theranostic application of nanostructures to explore the growth potential of this field, using this book as further reading
Udaykumar R. YaragattiProfessor (HAG)Electrical and Electronics Engineering DepartmentNational Institute of Technology Karnataka, Surathkal, IndiaandFormer DirectorMalaviya National Institute of Technology Jaipur, India
Preface
When I sat to pen this preface, I remembered Prof. Isaac Asimov, the great science fiction writer, who said “I believe that scientific knowledge has fractal properties, that no matter how much we learn, whatever is left, however small it may seem, is just as infinitely complex as the whole was to start with. That, I think, is the secret of the Universe.”
I felt the same while writing this book. This science of very small particles, seems to have infinite applications.
The birth of a new branch of science took place based on the effort to manipulate matter on atomic and molecular scales to create nanosized materials. These materials exhibited unique properties that were different from their bulk counterparts. This novel material found application in almost all the branches of science to develop products ranging from computers to biological micromachines. The application of nanotechnology in nanomedicine, an area that encompasses diagnostics and therapeutics. Nanomaterials have shown possibility in regulating the interface between materials and cells/tissues. Both inorganic and inorganic nanomaterials, such as metals, polymers, their hybrids and composites, are being utilized in nanomedicine.
Several research and review articles focusing on the contribution of different types of nanomaterial in nanomedicine have formed the basis of this book. It deals with the use of nanomaterials for combatting various diseases and disorders of the human body. The three chapters in the first part of this book deal with the areas in which nanotechnology has contributed to nanomedicine. In the second part, different disorders like cancer, neurodegenerative diseases, genetic diseases, infectious diseases, cardiovascular disorders, eye, dentistry, bone and cartilage affecting diseases are discussed. In chapters relating to a disease or disorder of a particular organ, a basic brief introduction to them is given. I must say it is not a book of medical sciences; whatever is mentioned in brief is only given to understand the areas in which the use of nanotechnology is discussed. There are still miles to go before the full potential of nanotechnology can be brought to the masses; I hope that this book will engender ideas in researchers as to which direction this should take.
The first chapter gives a brief introduction to the use of nanomaterials in prevailing diagnostics and the research being done to study the future possibility of the uses of nanotechnology. For diagnostic, the nanoparticles as well as quantum dots are being used as tools for in-vivo imaging. Molecular imaging using SPION (superparamagnetic iron oxide) and microcomputed tomography have also already been improved to be significant in magnetic resonance imaging.
For the second chapter, I wish to acknowledge Dr. Rupa Dharmatti of Texas A&M University who has elaborated the use of nanoparticles as a delivery vehicle of biological moieties such as genes, proteins, peptides and drugs. One of the major applications of nanotechnology has been realized with the capability of nanomaterials to mimic the role of scaffolds in tissue regeneration. The third chapter is about nanomaterials as smart scaffolds during regeneration of various damaged tissues. It touches upon the basic requirements of a scaffold and various types of natural and synthetic materials used as scaffold.
Chapters four to ten are about the research being done and some successful outcomes of the use of nanomaterials in different diseases and disorders, that includes diagnostics, nanoimaging, and therapeutics, including delivery systems and in some cases preventive approaches using nanomaterials. The major conerns about toxicity and biodegradability are also discussed in each chapter.
One of the misgivings of this book may be the very short introduction to the human organs. My account of this book is based on the use of nanotechnology for the diseases and disorders of various organs; therefore, I have presented just enough information about the anatomy of organs so that when applications of nanotechnology are discussed it could be correlated.
In conclusion, I will end with my view that nanotechnology is one of the largest pools of untapped resources, which with good intentions will translate into combatting diseases.
Madhuri SharonJune 2022
Part INANO-FLOTILLAS TRAVERSING IN THE VEIN AS CARRIERS TO DELIVER THERANOSTICS
1Diagnostic and Therapeutic Systems Using Nanomaterials
There is no standard therapeutic process, since there are so many different schools of therapy.
David D. Burns
1.1 Introduction
Both this book and chapter deal with therapy for various human disorders. Therapy is a word that is used for medical- or health-related treatments intended to relieve disorders. Hence, treatment and therapy can be considered synonyms Therapeutic remediation is associated with or depends on the diagnosis of health problems. The word “theranostic” is used to describe the combined efforts of diagnosis and therapy. Diagnostic and therapeutic devices or methods are often developed together. Useful devices are developed by working closely with the medical scientists who give input into a medical situation. For example, for oncotherapy, developing a therapy that is image guided so as to give localized treatment, especially for tumors and cancer; or image-guided catheters to inject chemotherapy directly into the blood vessels that feed a tumor, reducing the need for systemic chemotherapy.
In this chapter we will be discussing nanotherapy, which is a branch of nanotechnology that uses biocompatible nanoparticles as follows:
(i) To deliver a drug to a given target location in the body so as to treat the disease through a process known as targeted drug delivery [1];
(ii) For photodynamic chemotherapy [2];
(iii) Antibody-conjugated nanoparticles as a theranostic agent for ultrasound contrast imaging [3];
(iv) Targeted near-infrared (NIR) nanoparticles for photothermal therapy [4]; and
(v) Anticancer or oncotherapy by facilitating cancer cell apoptosis [5].
Drug delivery using nanoparticles and nanoconjugates as well as developing diagnostic devices using nanodiagnostic agents are the major areas of research related to the nanotherapeutic system.
Nanotechnology is already being used for early disease detection and diagnosis, treatment and prevention of disease, and precise and effective therapy [6]. Nanotechnology and various nanoparticles have exhibited potential for detecting disease indicators and markers of early precancerous cells, viruses, specific proteins and antibodies.
Nanodiagnostics involves molecular diagnosis, which helps in developing personalized cancer therapy. A nanodiagnostic device is based on pharmacogenetics, pharmacogenomics, and pharmacoproteomic information as well as environmental factors, which influence response to therapy. In the future, with the advancement in nanodiagnostic technologies, it will be a faster way of doing complete health checkups. Moreover, it will help in tailoring the required medication specifically to the individual based on their genetic makeup, which will prevent unwanted side effects.
1.2 Nanodiagnostic Agents
Nanodiagnostics involves molecular diagnosis, which is mostly used for personalized cancer therapy. This field is currently under development and being researched the world over. It involves the use of nanoparticles (carbon nanotubes, nanoshells, gold, and other metallic nanoparticles, nanopores, graphene, and cantilevers), quantum dots (semiconductor nanocrystals, exhibiting strong light absorbance property that can be used as fluorescent labels for biomolecules), etc., for rapid diagnostic tests and nanorobots as tools to make repairs at the cellular level. Personalized medicine for cancer therapy needs the desired biomarkers. Hence, another very important input of nanodiagnostic technologies that is being envisaged is to refine the discovery of biomarkers using nanoparticles because they have high surface area to volume ratio (SVR) and multifunctionality. nanodiagnostic approach will be future point‐of‐care (POC) diagnostics and monitoring technologies with the help of nanobiosensors and microarrays of biosensors-based biochip systems and microfluidic platforms for rapid diagnostic tests and rapid detection of various diseases or pathogen‐specific biomolecules/markers, such as DNA, proteins, whole cells (e.g., circulating tumor cells), etc. The nanotools will offer the fabrication of small‐scale portable devices.
The nanodiagnostic agents that are being researched are discussed in the following subsections for their applicability.
1.2.1 Bio-Barcode Assay (BCA)
Bio-barcode assay is already being used as a tool for rapid detection of protein-specific antigen (PSA), which is a marker for prostate and breast cancers [7]. It offers increased sensitivity and safety. For BCA assay, two different probes are used: (i) a magnetic microparticle conjugated to a PSA monoclonal antibody, and (ii) a gold nanoparticle to which a PSA polyclonal antibody and “barcode” oligonucleotides are attached. During the assay, PSA gets conjugated to gold nanoparticles (second probe) and becomes sandwiched between the two antibodies. Then, using magnet microparticle the antigen-containing complex is separated from the rest of the mixture. Here, the magnetic field draws the unbound magnetic microparticles to the walls of the container. The remaining particles that are left behind are involved in the detection. The separated complex is washed so as to de-hybridize the barcode oligonucleotides from the nanoparticle. The free oligonucleotides enable the detection of PSA. Using conventional DNA detection methods, barcode is detected. It is also detected by silver amplification method [8]. By this method, as low as 30 attomole/L in a 10 µL sample has been detected [7]. The sensitivity of this assay can be increased by manipulating the equilibrium of the reaction by changing the concentration of the magnetic microparticle probe (Figure 1.1).
1.2.2 Cantilever Beam
Cantilevers are a nanomechanical tool used in diagnostics. A cantilever beam is a beam which is anchored or fixed at only one end and the other end is free (Figure 1.2). The fixed end entirely resists the moments and shear generated by the loads acting on the beam. Beam that is fixed at one end cannot rotate or translate in the direction that load is applied. Whereas, the other end is free to rotate and translate in the direction of the applied load. Micromachined silicon cantilever beams are similar to those used in atomic force microscopy, function by use of nanomechanical deflections. Because the beam is anchored only on the one end, thermal expansion and ground movement are fairly simple to sustain.
Figure 1.1 Barcode assay of PSA using nanoparticles. A schematic representation of the PSA AuNP probes (upper); and the PSA bio-barcode assay (lower).(Upper) Barcode DNA-functionalized AuNPs (30 nm) are conjugated to PSA-specific antibodies through barcode terminal tosyl (Ts) modification to generate the coloaded PSA AuNP probes. In a second step, the PSA AuNP probes are passivated with BSA. (Lower) The bio-barcode assay is a sandwich immunoassay. First, MMPs surface-functionalized with monoclonal antibodies to PSA are mixed with the PSA target protein. The MMP-PSA hybrid structures are washed free of excess serum components and resuspended in buffer. Next, PSA AuNP probes are added to sandwich the MMP-bound PSA. Again, after magnetic separation and wash steps, the PSA-specific DNA barcodes are released into solution and detected using the scanometric assay, which takes advantage of AuNP catalyzed silver enhancement. Approximately ½ of the barcode DNA sequence (green) is complementary to the “universal” scanometric AuNP probe DNA, and the other ½ (purple) is complementary to a chip-surface-immobilized DNA sequence that is responsible for sorting and binding barcodes complementary to the PSA barcode sequence. (Source: Scheme 1 from C. Shad Thaxton et al., Nanoparticle-based bio-barcode assay redefines “undetectable” PSA and biochemical recurrence after radical prostatectomy. PNAS; 106(44): 18437–19442, 2009. Open access article ©2009 National Academy of Science).
Figure 1.2 A cantilever beam.
At present, cantilevers are one of the most promising technologies for clinical diagnosis. The micromachined silicon cantilevers are now being used for protein and DNA detection and quantification. The advantage of using a cantilever beam is that there is no toxicity concern. A standard cantilever biosensor can detect multiple target molecules from small biological samples especially for the detection of cancer at an early stage. Once a tumor becomes malignant, it is too late to treat the cancer with a maximum success rate. Since cancers spread through blood and particularly the lymphatic system in the body, it becomes important to measure multiple parameters of biological molecules. In a cantilever, biosensor biomolecules are adsorbed onto one side of the surface of the cantilever, causing a decrease in the surface free energy and generating a differential surface stress between either side of the cantilever beam as a result of adsorption of biomolecules occurring at one side of the cantilever. For DNA detection, the cantilever surface holds a particular DNA sequence capable of binding to a specific target. For DNA detection, at one side of the cantilever layer hybridization occurs between the target probes, changing the intermolecular interactions within a monolayer, which induces surface stress that bends the cantilever beam and initiates a motion (Figure 1.2). The deflection of the cantilever caused by surface stress change, which is in the range of several nanometers, is measured using a piezoelectric readout.
Based on the same principle, specific DNA strands are detected. Single-stranded DNA (ssDNA) is isolated using a cantilever sensor by coating one side of the cantilever surface with gold and applying a thiol linking agent at one end of the DNA (Figure 1.3). A variation of 3050 mN/m in surface stress occurs as a result of ssDNA adsorption. The process of surface stress is based on adsorption of sulfur atoms (sulfur atom acts as a receptor for a strand complementary to the DNA sequence) on the thiol agent attached to one end of the ssDNA that is also bound to the surface of the cantilever. The isolated DNA is then identified as noncomplementary strands that carry a mutation.
Figure 1.3 Cantilever beam response: (a) initial state and (b) sensing state.
Carbon nanotube (CNT) has a cylindrical and hollow tube shape and a number of walls enclosing a nanotube, making it single-walled carbon nanotube (SWCNT) or multi-walled carbon nanotube (MWCNT); and an arrangement of carbon atoms with respect to tube axis (there are many kinds of chiral tubes) makes it a suitable material for preparing a cantilever. Mechanical (such as bending or bucking and high resilience to mechanical strains) and thermal (it shows thermal expansion under temperature) properties of CNT shows that cantilever can be fabricated from it and used for detecting cancer. Moreover, MWCNTs can adsorb light energy selectively depending on light polarity.
1.2.3 Carbon Dots/Carbon Quantum Dots
Quantum dots (QDs) are semiconductor crystals having their excitons or electrons and holes confined in all three dimensions of space. Consequently, QDs have electronic properties that are intermediate between those of bulk semiconductors and those of discrete molecules. They are very small particles (size ranges from 1–10 nm) that follow wave theory concept. Being very small in size, they possess larger band gap. This is because of the discreet energy level, which depends on the size and shape of the QD [1]. Because of their various optical and electronic properties like excitation of multiple fluorescence spectra, enhanced photostability, high quantum yield, and photocatalysis, QDs are used as a tool for biological imaging, diagnostics, and molecular histopathology. Though there are many known inorganic QDs, such as cadmium telluride (CdTe), cadmium selenide (CdSe), lead selenide (PbSe), gallium arsenide (GaAs), gallium nitride (GaN), indium phosphide (InP), indium arsenide (InAs), etc., due to their cytotoxicity and insolubility in water they are not suitable for biological applications.
Figure 1.4 Transmission electron microscopy image of carbon dot.
Carbon dots, a new form of fluorescent carbon nanostructure (Figure 1.4), were discovered in 2004 by Xu et al. [9] and were termed as carbon quantum dots (CQDs) or carbon dots (CD), as they exhibited QD-like properties and characteristics such as they are. However, CDs are nontoxic, biocompatible, resistant to photobleaching, water soluble, and comparatively inexpensive to synthesize. For suitable application of CD as a theranostic agent it is often conjugated with other biogenic, organic or inorganic molecules [1] so as to get desired particle size and size distribution for the in-vivo distribution, stability, drug loading and drug release ability, uptake by cells, biological fate, toxicity; and the targeting ability of these delivery systems, availability to a range of cellular and intracellular targets, easy mobility and capacity to cross the blood-brain barrier to treat neurogenerative disorders. CDs are used as a tool for multiplexed diagnostics; Immunohistochemical assays; neurotransmitter detection; and cellular imaging. For this, CDs are used in electronic devices given below.
1.2.3.1 CD as Bioimaging Agent
Bioimaging is a noninvasive method to visualize biological processes in real time without interfering with the living processes, giving information on the 3D structure of the specimen from the outside, without physical interference. It has been used for imaging various cancer cells, bacteria, viruses, drosophila, etc.
1.2.3.2 CD as Sensor
Carbon dots exhibit photoluminescence (PL) emission in the near-infrared (NIR) spectral region under NIR light excitation. This property is useful as a sensor because of the transparency of body tissues in the NIR “water window.” The PL from CDs is efficiently quenched by both electron acceptor or electron donor molecules in solution, because photoexcited CDs are excellent electron donors and electron acceptors. This makes the CD-based sensor/detector very sensitive and selective. The quenching refers to decreases in the fluorescence intensity of CD due to fluorescence resonance energy transfer (FRET). The CDs are easily internalized in the cells and are stable, highly sensitive, show specificity and accuracy; and are versatile material for designing multifunctional biosensors to detect: (a) Metal ions – fluorescence “turn-off” assays have been used for the detection of metal ions (Hg2+, Cu2+, Pb2+, Fe3+, Ag+, and Cr6+, etc). (b) Small molecules for detection of small molecules (Nitric Oxide, Phosphate, Reactive Oxygen Species. H2S, Trinitrotoluene or TNT, Hydroquinone, Surfactant), instead of using fluorescence quenching mechanism, detection is done by restoring fluorescence of the quenched CDs. (c) Biological pH or Physiological pH are the pH value in living cells and tissues at which metabolic activities take place. It is determined by CDs by measuring the fluorescence intensity of the CD as it is highly sensitive to pH. CDs exhibit a strong emission at pH 7.0; whereas, under strongly alkaline or acidic conditions, the PL is nearly completely quenched [4]. Both in-vivo and in-vitro pH have been detected using CD as a tool [10]. The precursor for synthesis of CD plays an important role in its use for pH detection. For example, CD from ascorbic acid that exhibited a linear dependence on the pH of the solution in the range of 4.0 to 8.0 had potential application in colorimetric and fluorescent probes for pH measurement, generating a good linear calibration curve in the pH range from 6.0 to 8.0; whereas CD from citric acid displayed a good linear relationship with the solution pH value in the range of 2.55–5.19 and an excellent reversibility between pH 5 and pH 9 [11]. Another precursor, threonine-derived CD [12], has also shown that fluorescence of CDs was sensitive to pH in a broad range of 2.13–9.34. (d) Nucleic acid/DNA detection is done using different methods, one of them using methylene blue to quench the fluorescence of CDs; hence, ctDNA is joined in solution; the fluorescence of the solution was found to be restored. Based on this, a fluorescent sensor for DNA detection was designed; the detection limit was 1.0 × 10−6 mol/L with a linear range of 3.0 × 10−6 mol/L to 8.0 × 10−5 mol/L [13]. Another method of DNA detection is using KMnO4 to trigger chemiluminescence of CDs. The DNA detection was performed in a linear range from 10−18 to 10−14 mol/L with the low limit of detection being 8.56 × 10−19 mol/L [14]. There are several such methods being researched the world over. (e) Vitamin detection – so far riboflavin and vitamin B12 have been successfully detected by surface-functionalized CDs. It is done by CDs-based ratiometric sensor with high sensitivity of 1.9 nM for riboflavin. (f) Protein detection – Many different protein and enzyme detection sensors have used CDs such as an aptamer-functionalized CD [15]; a novel CDs-dsDNA sensor has also been developed to detect protein and enzymes [16], where PL is quenched in the presence of dsDNA to detect histone; addition of histone turns on the luminescence through unwinding dsDNA from CDs due to the strong affinity between histone and dsDNA. With the binding affinity between DNA and proteins, the quantitative detection of protein can be calculated from fluorescence restoration. Another turn-on, CDs-based nanosensor, is composed of CDs and gold nanoparticles for detection of cysteine with multiple signals. It has excellent selectivity and sensitivity [17]. (f) Sugar detection – CDs is used to detect glucose through peroxidase-like catalytic activity of CDs, which is achieved by assembling porphyrins on the surface of CDs by π-π stacking and electrostatic interactions [18]. The CDs catalyze the appropriated peroxidase substrate, producing a blue color in the presence of H2O2. However, this catalytic activity of modified CDs is temperature and pH (optimal pH was found to be 4.0) dependent but H2O2 concentrations do not affect it. The glucose oxidase immobilized CDs can detect glucose in the linear range from 20 μmol/L to 1 mmol/L with a detection limit of 7 μmol/L [19]. Therefore, CDs can be used for enzyme immobilization for several biomedical and technological applications.
1.2.4 Carbon Nanotubes (CNTs)
Since their discovery in 1992, carbon nanotubes have generated tremendous interest and efforts by scientists to look for their applications, resulting in applications being found in almost every branch of science. CNTs are allotropes of carbon having a mixture of sp3 and sp2 carbons with tubular graphenic structure that imparts semiconductor properties, the diverse geometries of which afford a spectrum of unique chemical, electrical, magnetic, and optical properties. Thus, a plethora of applications, which can be divided into two categories: (i) Applications of CNT in areaz other than biological systems; and (ii) Applications of CNT in biological systems.
Functionalization of CNT: For most of the applications, the CNT needs to be functionalized to increase its reactivity. CNTs are insoluble in water, polymer resins, and most solvents. Thus, they are difficult to evenly disperse in a liquid matrix. However, CNTs can be made soluble in both organic solvents and in aqueous solutions by organic functionalization. To utilize the CNTs’ novel physical properties in the manufacture of composite materials, as well as in other applications, it is necessary to physically or chemically attach certain molecules, or functional groups, to their sidewalls without significantly changing their desired properties. This process is called functionalization. Commonly, functionalization of CNT involves oxidation, fluorination, amidation, etc., either by attachment of organic moieties to carboxylic groups (that are formed by oxidation of CNT with strong acid) or by direct bonding to the surface double bonds. CNTs contain five-membered rings at the end of the tubes. These pentagonal carbons are oxidized by chemical treatments with suitable agents. Refluxing CNTs in a H2SO4/HNO3 mixture results in a clear, colorless solution, which upon removal of solvent and excess acid gives a white solid containing functionalized CNTs. Oxidized carbon atoms can act as specific sites for adsorption of metal ions (Figure 1.5). Treating CNT with suitable agents helps in attaching amid, amine, -COOH, and -OH groups, which are interesting materials for many biological applications.
The properties of CNTs, which have influenced its application in biosystems, includes their surface morphology, which makes them a suitable material for adsorption, absorption of gases and liquids, data storage, and template for the various biological reactions. Apart from surface morphology, electrical and electronic properties, and conducting and semiconducting properties make CNTs different from the other materials. The band gap of CNTs as well as their photochemical properties have found wide application in purification of water or degradation of organic and inorganic materials. Some of the successful applications of CNTs in diagnostics are discussed below.
Figure 1.5 A schematic diagram showing functionalization of CNT (having both ends opened) with –COOH.
1.2.4.1 Diagnostic Equipment Using CNT
Diagnostic equipment that uses CNTs as tools are: (i) Chemical sensors, (ii) Biosensors, (iii) Nanoprobes, (iv) DNA sensors, (v) Nanorobots, and (vi) X-ray devices.
1.2.4.1.1 Chemical Sensors Using CNT
Chemical sensors are those substances which change their surface conductivity when some specific materials get adsorbed at their surface. Surface conductivity depends on the ease with which electrons can migrate from cathode to anode (Figure 1.6).
The surface of any material contains either positively or negatively charged dangling orbitals. These sites are known as surface states. When electron migrates from cathode to anode, it encounters these surface states which hinder its transport to the anode. The conductivity of the surface depends on the surface states. When metal is exposed to other materials, adsorption of the materials occurs, which alters the percentage of dangling bonds present on the surface of metal. Hence, electrons moving on the surface alters the surface conductivity of the metal. The change in conductivity is related to the amount of material used for the adsorption; thus, one can find the concentration of the same material. The efficiency of this method depends upon the magnitude of change in conductivity with concentration.
Figure 1.6 (A) Dangling orbital shown by vertical lines present over a smooth metal surface; (B) Metal surface coated with CNTs. Each CNT possesses several dangling orbitals, thus increasing the concentration of surface states.
Moreover, there are single-walled carbon nanotubes (SWCNT) and multi-walled carbon nanotubes (MWCNT). The MWCNTs have been found to be very suitable electrode material for electrochemical sensors, as they have a wide electrical potential window, fast electron transfer rate, and large surface area; and are low cost and easy to use.
However, there have been reports of using SWCNT capacitor for chemical detection [20] because the capacitance of SWCNTs is highly sensitive to many chemical vapors and this transduction mechanism is used for a fast, low-power sorption-based chemical sensor. In the presence of a dilute chemical vapor, molecular adsorbates are polarized by the fringing electric fields radiating from the surface of a SWCNT electrode, which causes an increase in its capacitance. Hence, by thinly coating the SWCNTs with chemo-selective materials that provide a large, class-specific gain to the capacitance response, a high-performance, highly sensitive, fast and completely reversible gas sensor is constructed.
1.2.4.1.2 Biosensor Using CNT
As mentioned earlier, properties like its insolubility in water and possibility of cytotoxicity have been an obstacle during the course of investigation of biological uses of CNTs. As far as biological acceptability is concerned, there is a dispute: one group of scientists feels that it is toxic and another group advocates that it is not chemically toxic, but because of its small size it may be toxic; hence, depending upon the requirements, carbon can be used. To combat this problem, CNTs are functionalized by attaching biological molecules such as lipids, proteins, biotins, etc. Then they can usefully mimic biological functions, such as protein adsorption, and bind to DNA and drug molecules (Figure 1.7). This is expected to help in gene therapy and drug delivery. For biosensors, molecules, such as carboxylic acid (COOH), poly m-amino benzoic sulfonic acid (PABS), polyimide, and polyvinyl alcohol (PVA), have been used to functionalize CNTs. Functionalized CNTs can become soluble in water and other highly polar, aqueous solvents. Biosensors are already been used for bio-stress detection and for glucose and DNA detection.
Figure 1.7 Schematic diagram of CNT-based biosensor.
1.2.4.1.3 Nanoprobe Using CNT
Probes are devices for investigating and obtaining information on an unknown region. CNTs have been used for making probes [21, 22], e.g., AFM (atomic force microscope) probes. Conventional AFM tips are made of silicon or silicon nitride and are pyramidical in shape, having 5 nm radius of curvature. Moreover, nanoprobes made of CNTs have high resolution. As their cylindrical shape and small tube diameter enable imaging in narrow and deep cavities, they have mechanical robustness, which enhances the life of probes by minimizing sample damage during repeated hard crashes onto substrates and low buckling force; hence, they can be applied for imaging soft biological materials.
1.2.4.1.4 DNA Sensor Using CNT
For applications in diagnostics, vaccine, and drug delivery, or multi presentation of bioactive molecules, soluble CNTs are further derivatized by coupling with amino acids and bioactive peptides that are immobilized on the external walls of CNTs. Since CNT has very large surface to volume ratio, it contains large concentrations of “dangling bonds” which behave either like Lewis base or Lewis acid. The advantage of large dangling bonds is that chemicals can be temporarily loaded and unloaded from CNT, because dangling bonds help to form sort of a chemical bond which is not as strong as normal chemical bond (Figure 1.8). Therefore, CNTs are promising material for biomedical applications because one is able to tailor them for a specific purpose.
DNA is a coding molecule of living organisms that controls all the functions of the whole system. Therefore, since DNA can sense malfunctioning of the body parts, it can be used in nanosensors and CNT provides an excellent platform to attach DNA. Surface-confined MWCNTs have been shown useful in facilitating the adsorptive accumulation of guanine, a nucleobase which greatly enhances its oxidation signal. SsDNA/SWCNTFET sensors have been found to be very efficient and fast and can detect a variety of odors within a fraction of second.
Figure 1.8 Schematic of a CNT showing presence of dangling bonds due to electronically unsatisfied carbon present on the surface. During the formation of the material, electron may get lost from the surface, creating a +ve charge, or it may contain unsatisfied electrons such that overall surface behaves like a neutral surface.
1.2.4.1.5 Nanorobots Using CNT
Feynman’s talk, “There is Plenty of Room at the Bottom” indicated the possibility of a nanorobot. However, it is still in the R&D phase. Robotics is the use of technology to design and manufacture intelligent machines that can perform specifically programmed tasks. Nanorobots are nano size microscopic devices that work at the atomic, molecular, and cellular level. These devices are very sensitive to acoustic signals, hence can be programmed using sound waves to perform specific tasks. They are being researched for the purpose of maintaining and protecting the human body. When implanted into the bloodstream, these nanorobots can identify the cause of fever, the harmful cells and quarantine it, as well as provide the desired dose of medicine to the infected area; and can help in breaking up blood clots and kidney stones, and treat arteriosclerosis by breaking up plaque. Carbon in the form of diamond/fullerene is the principal element making up the bulk of a medical nanorobot. CNT is used for making smaller and faster components that will consume less energy and computerized parts will have high speed and high-capacity memory. Zhang et al. [23] have reported a carbon nanotube-based charge-controlled speed-regulating nanoclutch (CNT-CC-SRNC) composed of an inner carbon nanotube (CNT), an outer CNT, and the water confined between the two CNT walls, which proposes utilizing electrowetting-induced improvement of the friction at the interfaces between water and CNT walls. As the inner CNT is the driving axle, molecular dynamics simulation results demonstrate that CNT-CCSRNC is in the disengaged state for the uncharged CNTs, whereas water confined in the two charged CNT walls can transmit the torque from the inner tube to the outer tube. Importantly, the proposed CNT-CC-SRNC can perform stepless speed-regulating function through changing the magnitude of the charge assigned on CNT atoms. CNT-based actuators are used for high-technology applications such as humanoid robots, artificial and damaged hearts, artificial limbs, medical prosthetic devices, etc.
Another option is the use of molecular nanotechnology (MNT) or nanorobotics in surgery. In nanorobotics, surgeons move joystick handles to manipulate robot arms containing miniature surgical instruments at the ports. Another robot arm contains a miniature camera for a broad view of the surgical site. It results in less stress for surgeons and less pain for patients; at the same time, high precision and safety is achieved. MNT allows in-vivo surgery on individual human cells. Nanorobotics-based surgery can be used for gall bladder, cardiac, prostrate, bypass, colorectal, esophageal, and gynecological surgery. However, nanorobotic systems for performing surgery require the ability to build precise structures, actuators, and motors that operate at molecular level to enable manipulation and locomotion.
CNTs are also used as drug carriers for targeted drug delivery and for attaching to the body, preferentially similar to formation of bone tissue, etc. CNTs are also used for water and air filtration, hydrogen and energy storage.
1.2.4.1.6 X-Ray Devices Using CNT
Traditional X-ray is generated by heating a metallic filament (cathode) that emits accelerated electron, which is bombarded on a metal target (anode) to generate X-rays (Figure 1.9a). This X-ray generation method consumes high energy, has slow response time and has limited lifetime. Romero et al. [24] have reported that field emission is a better mechanism of extracting electrons than thermionic emission because electrons are emitted at room temperature, the output current is voltage controllable and the voltage necessary for electron emission is less. An optimal cathode material should have high melting point, low work function, and high thermal conductivity. CNTs meet all these requirements and hence are used as a cathode material for generating free-flowing electrons.
Figure 1.9 Schematic diagram of (a) Traditional method of generating X-rays; (b) CNT-based microfocus X-ray tube.
Electrons are readily emitted from their tips either due to oxidized tips or because of curvature when a potential is applied between a CNT surface and an anode. Continuous and pulsed X-rays can be generated using a CNT-based field emission cathode (Figure 1.9b) [25], which has fast response time, fine focal spot, low power consumption, can be miniaturized, has longer life, minimizes the need for cooling, and is low cost. Moreover, miniaturized X-ray devices can be inserted into the body by endoscopy to deliver precise X-ray doses directly at a target area only.
1.2.4.1.7 Surgical Supplements Using CNT
The surgical supplements or surgical aids that use CNTs as tools are: Nanomedicinal devices, bioactive nanomaterial in bone grafting, nanotweezers, etc. Surgical supplements are being designed to reduce the surgery using macro instruments that are cumbersome for both the surgeon and the patient, that may lead to surgical error due to the surgeon’s fatigue; moreover, macro surgical instruments are not suitable for certain delicate surgeries such as surgeries related to the heart, brain, eyes, and ears. Using CNTs, R&D is on the way to investigate smart instruments such as forceps, scalpels, and grippers with embedded sensors to provide improved functionality and real-time information to aid surgeons. CNTs are expected to be useful for optically guiding surgery, leading to easy removal of tumors and other diseased sites.
1.2.4.1.8 Nanotweezers Using CNTs
Carbon nanotube-based nanotweezers have already been created for manipulation and modification of biological systems such as structures within a cell; moreover, they have the potential to be used in medical nanorobotics also. These nanotweezers can be used (i) for manipulation and modification of biological systems such as DNA and structures within a cell, (ii) as nanoprobes for assembling structures, (iii) to aid in increasing the value of measurement system, (iv) and, as demonstrated, nested CNTs can make exceptionally low-friction nanobearings [26]. There is a need to investigate the use of CNTs as nanoprobes for crossing into the tumor, but not crossing into healthy brain tissue.
1.2.4.1.9 CNT as Tool for Tissue Engineering (TE)
Tissue engineering involves replacement of anatomic structure of the damaged, injured or missing tissue or organs by agglomerating biomaterials, cells and biologically active molecules (Figure 1.10) [27, 28]. The 3D scaffold of biomaterials provides mechanical support to the growing cells or tissue that can then be transplanted into the system. The schematic approach shown in Figure 1.10 demonstrates how tissue engineering uses a biomaterial scaffold to directly grow the body’s own cells in a lab and then implants the cells back into the body. The scaffold directs cell behavior, e.g., migration, proliferation, differentiation, maintenance of phenotype and apoptosis, by facilitating sensing and responding to the environment via cell matrix communications and cell-cell communications [29, 30].
Scaffold should have highly porous surfaces so as to allow seeding of cells at high densities as well as facilitating proper cell-cell interaction through a regulated molecular myriad [31]. Carbon nanotube has potential for multiple uses in tissue engineering [32]. Both SWCNT and MWCNT possess properties such as ordered structures with high aspect ratio, ultralight-weight, high mechanical strength, high electrical and thermal conductivity, metallic or semi-metallic behavior, and high surface area. These properties have made CNTs a favorite material for nanofabrication of compatible biomaterials which can act as scaffold for engineering tissues [33]. The areas where CNTs have significant relevance for tissue engineering are:
Figure 1.10 Schematic representation of use of tissue engineering on a scaffold and then implant it in the desired organ of the body. (Source: Carbon Nanofibers, Ed. Sharon and Sharon 2020, Wiley-Scrivener).
(i) Cell tracking and labeling; CNTs are feasible as imaging contrast agents for optical labeling, magnetic resonance, and radiotracer modality;
(ii) Monitoring cellular physiology;
(iii) Regulating cellular behavior; and
(iv) Structural support for tissue engineering.
1.2.4.1.10 Gene Delivery Using CNT
For gene delivery inside a cell or cell organelles, nano-sized devices that can pass through the delicate cell membrane without damaging it are needed. Since CNTs have needle-like geometry, high elasticity and strength, Gao et al. successfully used amino-functionalized MWCNTs for gene delivery [34], as it interacted with negatively charged DNA and the cell membrane and delivered the GFP (green fluorescent protein) gene into mammalian cells without any cytotoxicity. Simultaneously, Pantarotto et al. [35] also found that functionalized, positively charged, water-soluble CNTs can penetrate into cells and transport plasmid DNA by formation of noncovalent DNA-CNT complexes; giving the possibility that CNTs can be used as novel non-viral delivery systems for gene transfer. Chen and Rajewsky [36] have also shown that a CNT-based “nanoinjector” can penetrate a cell without damaging the membrane, even after repeated use. Later, Pan et al
