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- Herausgeber: John Wiley & Sons
- Kategorie: Fachliteratur
- Sprache: Englisch
This book is a comprehensive guide on the new-generation nanoengineered materials’ contribution to the ongoing development of medical devices and other healthcare applications.
Nanotechnology has revolutionized cutting-edge medical approaches, including gene therapy, targeted drug delivery, treatment of various chronic and genetic diseases, cancer diagnosis and treatment modalities, and more, leading to the establishment of personalized treatment regimens. The book reports on various nanoparticles, such as metallic and non-metallic nanoparticles, nano-micelles, liposomal nanoparticles, and polymer nanoparticles, being utilized in various aspects of medical and healthcare applications. In addition, novel natural product-based nanomaterials and nanomaterial complexes are also detailed, showing their potential applications. The impact of nanotechnology in promoting bone regeneration and serving as novel dental implants is investigated, along with its applications in skincare. The book examines the crucial role nanotechnology plays in the development of various antimicrobial materials and surfaces, which are being used in the medical sector, including numerous types of wound healing materials, antimicrobial textiles, and PPEs, as well as face masks and gloves. The book concludes with a chapter on nano-coated medical devices.
Audience
The audience comprises researchers, engineers, and scientists in materials science, nanotechnology, and bioengineering working in the biomedical and bioscience areas and industries.
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Seitenzahl: 583
Veröffentlichungsjahr: 2025
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Table of Contents
Cover
Table of Contents
Series Page
Title Page
Copyright Page
Preface
1 Nanomedicine—History and Recent Trends
List of Abbreviations
1.1 Introduction
1.2 Definition
1.3 History
1.4 The Main Aim and Recent Trends
1.5 Challenges
1.6 Current Status and Future Perspectives
1.7 Conclusion
References
2 Nanoparticles and Micelles as Biomedicine
2.1 Nanoparticles
2.2 Nanoparticles as Biomedicine
2.3 Micelles as Biomedicine
2.4 Conclusion
References
3 Natural Product-Based Nanomedicine
List of Abbreviations
3.1 Introduction
3.2 Natural Product
3.3 Natural Product-Based Nanomedicine
3.4 Conclusion
References
4 Engineered Liposomal Nanoparticles and Their Medical Applications
4.1 Introduction
4.2 Liposome Nanoparticles and Their Different Types
4.3 Ethosomes (Ethanolic Liposomes)
4.4 Types of Engineered Liposomal Drug Delivery Platforms
4.5 Medical Applications of Engineered Liposomes
4.6 Challenges and Limitations
4.7 Conclusions
Acknowledgment
References
5 Development and Characterization of Polymer Nanocomposites for Clinical Applications
Abbreviations
5.1 Introduction
5.2 Polymer Nanocomposites
5.3 Synthesis of Polymer Nanocomposites
5.4 Characterization Techniques
5.5 Clinical Applications of Polymer Nanocomposites
5.6 Polymer Nanocomposites for Clinical Application
5.7 Conclusion
5.8 Future Perspective
Acknowledgment
References
6 Bionanocomposites for Clinical Applications
6.1 Introduction
6.2 Raw Materials Used for Bionanocomposites Preparation
6.3 Bionanocomposite Application in the Clinical Field
Conclusion
References
7 Nanomodified Polymers for Bone Regeneration and as Dental Implant
List of Abbreviations
7.1 Introduction
7.2 Nanomodified Polymers
7.3 Nanomodified Polymers for Bone Regeneration
7.4 Nanomodified Polymers for Dental Implants
7.5 Conclusion
References
8 Stimuli-Responsive Nanoengineered Scaffolds in Medicine and Healthcare
Abbreviations
8.1 Introduction
8.2 pH-Responsive Nanoengineered Scaffolds
8.3 Light-Responsive Nanoengineered Scaffolds
8.4 Redox-Responsive Nanoengineered Scaffolds
8.5 Magnetic-Responsive Nanoengineered Scaffolds
8.6 Electro-Responsive Nanoengineered Scaffolds
8.7 Limitations and Challenges
8.8 Conclusion
References
9 Skin Care Applications of Nanomaterials
9.1 Introduction
9.2 The Use of Nanomaterials in Skin Care
9.3 Different Types of Nanomaterials Used in Cosmetics
9.4 Frequently Used Nanotechnology-Based Cosmetic Products
9.5 Future Goal
9.6 Conclusion
References
10 Nanocoated Wound Healing Materials
10.1 Introduction
10.2 Physiology of Wound Healing
10.3 Significance of Nanoparticles in Wound Healing
10.4 Nanoparticles Used for Wound Healing
10.5 Limitations
10.6 Future Perspectives
10.7 Conclusion
Acknowledgment
References
11 Nanomaterial Based Medical Textiles for Antimicrobial Applications
List of Abbreviations
11.1 Introduction: Medical Textiles
11.2 Microorganisms
11.3 Antimicrobials
11.4 Nanomaterials
11.5 Conclusions
References
12 Nanotechnological Advancements in the Development of Antimicrobial PPE
List of Abbreviations
12.1 Introduction
12.2 Gloves
12.3 Face Masks and Respirators
12.4 Coveralls
12.5 Conclusions
References
13 Nanotechnology-Enabled Face Masks for Improved Medical Applications
List of Abbreviations
13.1 The Era of Infections and the Need for Improved Masks
13.2 Manufacturing Methods for Mask Fabrics
13.3 Common Masks and Respirators in Healthcare Systems
13.4 Nanofibers
13.5 Nanoporous Membranes
13.6 Nanocoatings
13.7 Advances in Nanotechnology-Based Face Masks During the COVID-19 Pandemic
13.8 Are They Ready to Use?
References
14 Nanocoated Medical Devices: Prospects and Challenges
List of Abbreviations
14.1 Introduction
14.2 Timeline of Nanocoating in Medicine
14.3 Nanocoating in Diagnostics and Disease Management
14.4 Nanocoating in Surgery
14.5 Nanocoated Implants
14.6 Risks and Challenges of Nanocoated Devices in Medicine
14.7 Future Perspectives of Nanocoated Devices
14.8 Conclusion
References
Index
End User License Agreement
List of Tables
Chapter 3
Table 3.1 Physiological activity of nanoparticles.
Table 3.2 Biosynthetic pathways of metabolites.
Table 3.3 Research studies on polymer nanoparticles (micelles, liposomes, and ...
Table 3.4 Nanomedicine waste effects on a human being.
Table 3.5 Modification of drug-release properties and controlled targets.
Chapter 4
Table 4.1 Liposome classification based on their preparation with size and str...
Table 4.2 Conventional methods used in the formulation of different types of l...
Table 4.3 Some marketed formulations based on liposomes [38–40].
Table 4.4 Formulations of transfersomes with their outcomes.
Table 4.5 Medical applications of engineered liposomes with classifications.
Table 4.6 Stealth liposome applications.
Table 4.7 Biomimetic liposome applications.
Chapter 6
Table 6.1 Bionanocomposites for dental applications.
Table 6.2 Bionanocomposite application in targeted drug delivery.
Table 6.3 Theragnostic applications of bionanocomposites in cancer.
Table 6.4 Bionanocomposite-based sensors for glucose detection.
Table 6.5 Bionanocomposite-based diabetic wound-healing materials.
Table 6.6 Bionanocomposites for various orthopedic applications.
Chapter 7
Table 7.1 Alginate-based nanocomposites for bone regeneration.
Table 7.2 Cellulose-based nanocomposites for bone regeneration.
Table 7.3 Chitosan-based nanocomposites.
Chapter 9
Table 9.1 Various roles and purposes of skin care in the cosmetics industry.
Table 9.2 Types of nanotechnology-based cosmetic products frequently used and ...
Table 9.3 A list of nanotechnology-based cosmeceuticals on the market.
c10
Table 10.1 Studies showing the usage of silver nanoparticles for wound healing...
Chapter 13
Table 13.1 Properties of common respirators based on different standards.
List of Illustrations
Chapter 1
Figure 1.1 The boundaries between nanobiotechnology and nanomedicine.
Figure 1.2 Application of nanomedicine within healthcare.
Figure 1.3 The main components of a biosensor.
Figure 1.4 Theranostics can be considered as the combination of diagnosis, tre...
Chapter 3
Figure 3.1 Schematic representation of nanoparticles.
Chapter 4
Figure 4.1 A diagrammatic representation of (a) Liposome and (b) Transfersome....
Figure 4.2 The mechanisms of action showing how lipid vesicles permeate the sk...
Figure 4.3 Types of liposome surface modifications for drug delivery systems [...
Figure 4.4 Medical applications of engineered liposomes.
Chapter 5
Figure 5.1 The schematic representation of the formation of silver and gold na...
Figure 5.2 Schematic representation of an electrospinning setup where doped po...
Figure 5.3 Different clinical applications of polymer nanocomposites.
Chapter 6
Figure 6.1 Types of biopolymers and their origin.
Figure 6.2 Various applications of bionanocomposites in the clinical field.
Figure 6.3 Schematic representation showing the fabrication of dental resin co...
Figure 6.4 Illustration of controlled drug delivery mediated by bionanocomposi...
Figure 6.5 Schematic representation of (a) the three types of prepared bionano...
Figure 6.6 Illustration showing (a) the fabrication of the GOx@PAVE-CNTs biose...
Figure 6.7 Schematic representation of (a) halloysite nanoparticles loaded wit...
Figure 6.8 Schematic illustration of (a) an Edaravone (EDA)-loaded alginate bi...
Figure 6.9 Schematic representation of bionanocomposites for bone tissue engin...
Figure 6.10 Schematic representation of nBG/PU and nMBG/PU scaffolds and their...
Chapter 9
Figure 9.1 Different nanomaterials: nanoparticles, liposomes, nanoemulsions, s...
Chapter 10
Figure 10.1 Different stages of the wound-healing process.
Figure 10.2 The schematic representation of the different nanomaterials used i...
Chapter 13
Figure 13.1 Manufacturing methods for mask fabrics and common types of materia...
Figure 13.2 Melt-blowing process.
Figure 13.3 Spun-bonding process.
Figure 13.4 Electrospinning process.
Figure 13.5 Schematic of face mask (a) and surgical mask (b).
Figure 13.6 Dip coating process.
Chapter 14
Figure 14.1 (a) Nanopatterned chips and (b) porous NPs.
Figure 14.2 Quantum dot nanocrystal.
Figure 14.3 Lipid NP-encased biomolecules and act as nanocarriers.
Figure 14.4 (a) Porous NPs and (b) nanospheres. The innermost cavity (gray) ho...
Figure 14.5 Polymeric NPs that carry hydrophobic drug particles.
Guide
Cover Page
Series Page
Title Page
Copyright Page
Preface
Table of Contents
Begin Reading
Index
WILEY END USER LICENSE AGREEMENT
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Scrivener Publishing100 Cummings Center, Suite 541JBeverly, MA 01915-6106
Publishers at ScrivenerMartin Scrivener ([email protected])Phillip Carmical ([email protected])
Nanoengineered Materials for Medical and Healthcare Applications
Edited by
Radhakrishnan E.K.
School of Biosciences, Mahatma Gandhi University, Kottayam, Kerala, India
Ashitha Jose
School of Biosciences, Mahatma Gandhi University, Kottayam, Kerala, India
and
Visakh P.M.
Department of Chemical Oceanography, School of Marine Sciences, Cochin University of Science and Technology, Cochin, Kerala, India
This edition first published 2025 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© 2025 Scrivener Publishing LLCFor more information about Scrivener publications please visit www.scrivenerpublishing.com.
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Library of Congress Cataloging-in-Publication Data
ISBN 978-1-119-79164-5
Front cover images courtesy of Wikimedia CommonsCover design by Russell Richardson
Preface
Nanotechnology has already demonstrated an extensive role in the medical and healthcare sectors, bringing about various novel innovations that positively impact the quality and efficacy of diagnosis and treatment alike. Thus, the impact of nanotechnology on the medical field is regarded as a leading hotspot, resulting in enhanced drug-loading efficacy, novel drug biocompatibility, and better-targeted transportation. This, in turn, can not only advance drug efficacy but also minimize inadvertent side effects. The emergence of novel nanostructures with unique physicochemical properties plays an astounding role in the medical field. Nanotechnology has revolutionized cutting-edge medical approaches, including gene therapy, targeted drug delivery, treatment of various chronic and genetic diseases, cancer diagnosis and treatment modalities, and more, leading to the establishment of personalized treatment regimens. Even so, these interventions can still be considered in their early stages, where further research plays a crucial role in determining the extent of possible development and successful applications.
Various nanoparticles, such as metallic and non-metallic nanoparticles, nano-micelles, liposomal nanoparticles, and polymer nanoparticles, are being utilized in various aspects of medical and healthcare applications. In addition, novel natural product-based nanomaterials and nanomaterial complexes are also being explored for their potential applications, providing an added advantage to existing medical systems. The impact of nanotechnology in promoting bone regeneration and serving as novel dental implants has been further investigated, along with its applications in skincare. Nanotechnology plays a crucial role in the development of various antimicrobial materials and surfaces, which are being used in the medical sector. This includes numerous types of wound healing materials, antimicrobial textiles, and PPEs, as well as face masks and gloves. These novel products have been widely appreciated and accepted during the recent pandemic outbreak.
Even though nanoparticles have a significant impact on medical and healthcare applications, their toxicity, accumulation, and elimination from the body must be thoroughly evaluated to ensure the safety of both patients and practitioners. Despite these considerations, the impact of nanotechnology on the healthcare and medical sectors remain indisputable and is being further explored. This book reviews the impact of nanotechnology across various aspects of medical and healthcare applications. Contributors have been chosen from among worldwide experts in the respective subject areas, enhancing the book’s value. Additionally, a detailed index is provided for reference. The editors are grateful to all the contributors of this book, and special thanks also go to Martin Scrivener and Scrivener Publishing for their support and publication.
The Editors
November 2024
1Nanomedicine—History and Recent Trends
Sohrab Nikazar1* and Hedieh Haji-Hashemi2
1Chemical Engineering Faculty, Engineering College, University of Tehran, Tehran, Iran
2Department of Electronic Engineering, Universitat Rovira I Virgili, Tarragona, Spain
Abstract
The recent extraordinary advances in nanotechnology have paved the way for the development of nanomedicine—the application of nanotechnology in the medical field. The field of nanomedicine involves therapeutics or disease therapy, drug delivery, diagnostics and imaging, and regenerative medicine utilizing molecular tools. It can create remarkable opportunities and potential to solve challenges in numerous medical and health-related issues. This chapter illustrates the basic principles, brief history, and current progress of the nanomedicine field as well as proposes a short perspective for the future.
Keywords: Nanomedicine, nanotechnology, therapeutics, drug delivery, nanomedicine
List of Abbreviations
AI
Artificial intelligence
CNS
Central nervous system
CT
Computed tomography
EMA
European medicines agency
EPR
Enhanced permeability and retention
FDA
Food and Drug Administration
FIM
Field electron microscope
IR
Infrared
MDR
Multidrug resistance
MRI
Magnetic resonance imaging
NIH
National Institutes of Health
NIR
Near-infrared
PDT
Photodynamic therapy
POC
Point-of-care
PTT
Photothermal therapy
TEM
Transmission electron microscope
1.1 Introduction
Merging nanotechnology, a world-shaking field of science, and medicine has led to new approaches and strategies for designing specialized pharmaceutical formulations. Nanomedicine, being a product of nanotechnology, is a promising research field that has attracted significant attention around the globe and across multiple disciplines.
Nanomedicine involves therapeutics or disease therapy, drug delivery, diagnostics and imaging, and regenerative medicine utilizing molecular tools. There are numerous medical conditions such as cancer, cardiovascular disease, endocrine diseases like diabetes, and other infections which have found cures through nanomedicine [1, 2]. Nanomedicine has emerged to meet the medical challenges that conventional methods failed to solve properly, such as early and rapid diagnosis, targeted and effective drug delivery, and novel ways of providing organ and tissue replacement. Utilizing nanomedicine can diminish the side effects of traditional drugs and improve their efficacy. The unique properties and features that nanomaterials possess at nanoscale result in unique medical outcomes, such as increased bioavailability and minimal side effects, and aid in controlling cellular molecular processes and clinical translation.
In order to successfully translate nanomedicine, massive preclinical research, careful clinical trials, and appropriate clinical indications are required. This development process is time-consuming. Although its current translation state is unsatisfactory and not efficient enough, continuous and fruitful research activities on nanomedicine are leading to constant progress toward the goal.
This chapter gives an overview of nanomedicine and the recent developments in the field. First, the definition, brief history, and development of nanomedicine are presented. Afterward, the main aim of employing nanomedicine as well as its recent trends and applications are discussed in detail. Last but not least, the challenges and limitations ahead of nanomedicine product development and commercialization are pointed out. This chapter is dedicated to all those who are interested in this area and eager to take a broad view of the field.
1.2 Definition
Nanomedicine can be defined as the application of nanotechnology in medicine and is a key science of the 21st century.
Modern nanotechnology is an interdisciplinary science concerning the special chemical, physical, and mechanical properties of nanoparticles and their application in biology, chemistry, physics, medicine, electronics, and information technology. The evolution of nanoscience and nanotechnology has begun to adjust the foundations of disease diagnosis, treatment, and prevention. The National Institutes of Health (NIH) in Bethesda, MD, USA considered these scientific and technological innovations as nanomedicine.
Nanomedicine as a modern interdisciplinary science was first established in the nineties of the last century, and it developed rapidly, driven by tremendous progress in techniques [3]. This field has attracted scientists around the globe and across multiple disciplines.
Currently, there is no generally agreed definition for nanomedicine due to its blurred borderlines and boundaries [4]. In some cases, nanomedicine encompasses both biotechnology and microsystem technology; therefore, the definition of nanomedicine sometimes seems ill-defined, and interpretations of the term may vary.
The European Science Foundation and the European Technology Platform on Nanomedicine do not refer to the nanoscale dimensions in the definition of nanomedicine, while the US National Nanotech Initiative clearly refers to it. These definitions are as follows:
The European Science Foundation: The field of nanomedicine is the science and technology of diagnosing, treating, and preventing disease and traumatic injury, relieving pain, and preserving and improving human health, using molecular tools and molecular knowledge of the human body [5].
The European Technology Platform on Nanomedicine: Nanomedicine is defined as the application of nanotechnology to health. It exploits the improved and often novel physical, chemical, and biological properties of materials at the nanometric scale. Nanomedicine has a potential impact on the prevention, early and reliable diagnosis, and treatment of diseases [6].
The US National Nanotech Initiative: Nanomedicine is the application of nanotechnology to medicine. Nanotechnology is the understanding and control of matter at dimensions between approximately 1 and 100 nanometers, where unique phenomena enable novel applications. Encompassing nanoscale science, engineering, and technology, nanotechnology involves imaging, measuring, modeling, and manipulating matter at this length scale [7].
In general, two concepts can be distinguished. One of these concepts considers nanomedicine very broadly as a technology that uses molecular tools and knowledge of the human body for medical diagnosis and treatment [8], while the other concept emphasizes the original meaning of nanotechnology as making use of physical effects occurring in nanoscale objects in which quantum mechanics still reigns [9].
Here, the second concept is considered, and nanomedicine is defined as the use of nanoscale or nanostructured materials in medicine that, according to their structure, have unique medical effects, although these medical effects are not restricted to a size range below 100 nanometers. The attractiveness of nanomedicine applications lies in the unique characteristics of three-dimensional constructs with multiple components on the nanoscale.
1.3 History
Nanomedicine is considered a relatively young science that branched from nanotechnology at the beginning of the 20th century. Nanotechnology emerged after the invention of high-resolution microscopy in the early 1900s. Afterward, simultaneous research and efforts have been made in various new disciplines that branched from nanotechnology. In fact, nanoporous ceramic filters, as the first nanomaterials, were already known and applicable to separate viruses in the 19th century. Nevertheless, the first theoretical evidence on nanoparticles was established by Max Planck and Albert Einstein. They could have confirmed the presence of these tiny particles, although the lack of necessary instruments prevented them from these particles visible [3].
Developing the transmission electron microscope (TEM) in 1931 diminished the utilization of commonly used light which was not able to provide an insight into the atomic range [10]. Erwin Müller then developed the field electron microscope (FIM) leading to the observation of atoms and their arrangements. Afterward, huge advancements, especially in chemistry and biology, such as the discovery of cell structure and constituents, understanding of mechanisms maintaining and regulating metabolism, and understanding of DNA and RNA, were achieved with the aid of using the innovative microscopes [11–13].
At the beginning of the 1980s, scanning probe microscopy provided the opportunity to see objects in the nano range. In 1981, the scanning tunneling microscope (STM), developed by Gerd Binnig and Heinrich Rohrer, made an atom visible successfully [13]. Utilizing a variety of scanning probe microscopy methods, the nanoscale structures were demonstrated clearly and precisely followed by the possibility of manipulating and positioning them in a controlled way. As a result, new scientific disciplines arose, which were mainly tailor-made to the nano range. Norio Taniguchi proposed the term “nanotechnology” and its definition1 in 1974, which is still valid to this date [14].
Nanotechnologies and their applications were predicted by Richard P. Feynman, the physicist and Nobel prize winner. In 1959, he published a paper entitled “There’s Plenty of Room at the Bottom: An Invitation to Enter a New Field of Physics.” Although he did not use the term “nano” in his paper, it is regarded as the founding text of nanotechnology. He invited scientists to consider quantum mechanics for the production and control of tiny machines. He even mentioned the use of these tiny machines in medicine.
After Feynman’s revolutionary statements, scientists followed two main policies for producing nanostructures. The top-down approach deals with stepwise size reduction of existing machines. On the other hand, the bottom-up approach concerns the nanostructures’ construction atom by atom which is called molecular engineering. The theory of producing nanostructures from individual atoms using and controlling the self-organizing forces of atoms and molecules became popular in 1986, specifically after the first book on nanotechnology was published. K. Eric Drexler discussed this theory in “Engines of Creation: The Coming Era of Nanotechnology.” The possible application of nanotechnology in medicine and specifically the term “nanomedicine” was first described in the book “Unbounding the Future: The Nanotechnology Revolution” in 1991. The term came into technical literature in 1999 with the book “Nanomedicine” by Robert A. Freitas [3].
Paul Ehrlich made the first attempts to develop bullets carrying drugs to target diseases and kill pathogens after a single treatment at the beginning of the 20th century. This can be regarded as the beginning of chemotherapy, which later became possible in more sophisticated ways. Peter Paul Speiser was the first researcher to produce nanoparticles capable of performing targeted drug therapy at the end of the 1960s [15]. In the next decade, Georges Jean Franz Köhler and César Milstein managed to produce monoclonal antibodies. Since then, intensive research has been focused on the possible syntheses and uses of various carrier systems and the physicochemical functionalization of their surface structure. At the start of the 1990s, the transport of DNA fragments and genes by nanoparticles became possible for the first time [3, 13, 15].
Since 2000, significant developments in nanomedicine have been observed which paved the way for its technological and industrial development. In the early 2000s, many financial investments and funding have been granted to organizations to undertake some crucial tasks (e.g., providing strategic reviews on the nanomedicine status, assessing better potential healthcare opportunities, analyzing new technologies benefits, and determining future funding priorities).
In 2003, the European Science Foundation concluded a foresight study entitled “Forward Look on Nanomedicine” discussing the remarkable advances and developments that nanomedicine would offer in disease diagnosis and treatment. In 2004, the vision for nanomedicine research priorities was prepared by the High-Level Group European Technology Platform Nanomedicine, a group composed of 40 experts by the Commission of the European Communities. In the US, the NIH published its first nanomedicine roadmap in 2004 and established a national network of eight Nanomedicine Development Centers within two years. Their goals were to determine the nanoscale design principles and to use these principles in different areas of nanomedicine, such as tissue repair, disease cure, and cancer therapy [16].
The diagnostic and therapeutic sector of nanotechnology has attracted significant attention, which can be confirmed by the rapidly growing number of publications in this field. Its historical progress is made of three main stages: (1) 1964-1995: from the discovery of liposome structure to first approved nanotherapeutic, (2) 1995-2007: clinical validation and commercialization of some nanotherapeutics, and (3) 2008-present: rapid progress in new nanotherapeutics expansion [17].
1.4 The Main Aim and Recent Trends
Nanotechnology occurs at the interface between physics and chemistry, and its advancements are expected to have a growing impact on life sciences. Almost all the natural sciences could benefit from the unique characteristics that nanotechnology offers [18]. In medical sciences, nanotechnology can be applied in various areas, specifically in diagnostics, therapeutics, and regenerative medicine. It also has the potential to fundamentally change medicine in the coming decades.
To have a better understanding of the aim and applications of nanomedicine, we need to first shed light on the boundaries between nanomedicine and nanobiotechnology. Nanobiotechnology deals with molecular intracellular and intercellular processes that are vital in the application of nanotechnology in medicine. Figure 1.1 shows the diverse interplay between medically relevant nanotechnology and the possible applications of nanobiotechnology in human medicine. Although nanobiotechnology and nanomedicine concepts are related in certain aspects, these two fields have different applications. Nanobiotechnology encompasses all basic research at a nanoscopic level in biological systems, (e.g., investigations on plants) while nanomedicine focuses on the applications of nanotechnology concepts to medical applications [3].
As mentioned above, nanomedicine is expected to improve the currently available diagnostic, therapeutic, and regenerative techniques in medicine. Research in this field is focused on the design and fabrication of rapid diagnostic techniques (e.g., inexpensive rapid tests for genetic predisposition, rapid tests for early diagnosis of viral infections, and techniques for recording the first signs of diseases long before symptoms manifest themselves), production of medicines and vaccines without side effects (e.g., effective medicines for the treatment of cancer, cardiovascular diseases, and neurological diseases such as Alzheimer’s and Parkinson’s diseases), establishing of long-lasting and well-tolerated organ implants, and stimulation of neuronal activities. Indeed, research on finding novel diagnostic agents via intravenous and interstitial routes of administration, intelligent delivery and targeting of pharmaceuticals, and establishing novel implants is at the forefront of projects in nanomedicine.
Figure 1.1 The boundaries between nanobiotechnology and nanomedicine.
It can be concluded that the main aim of nanomedicine is to push the boundaries of the current diagnosis, therapy, and follow-up technologies, and thus, improve the available ‘find, fight, and follow’ methods in medical sciences. The ‘find, fight, and follow’ concept covers early diagnosis, therapy, and therapy control, which encompass the concept of theranostics. For example, appropriate contrast agents for imaging a single cell (‘find’), delivery of therapeutic drugs (‘fight’), and monitoring of the therapeutic development (‘follow’) are key issues of future medical care [19]. Figure 1.2 shows the current application of nanomedicine within healthcare.
1.4.1 Medical Diagnostics
Diagnostics have a vital role in medicine. Early identification of diseases and subsequent rapid treatment are of paramount importance to improve patient outcomes [20]. For some diseases such as cancer, early diagnosis is essential for successful prevention and efficient treatment. In the case of infectious diseases, the early detection of infection and the determination of its etiology is critical to improving patient outcomes, controlling the spread of disease, and decreasing antibiotic resistance [21]. Diagnostic methods in medicine have to be fast, highly sensitive, highly selective, convenient, reliable, and inexpensive. Also, miniaturization, parallelization, integration, and automation are of paramount importance. These requirements can only be fulfilled with the aid of nanotechnology. The advantage of using nanotechnology in diagnostics lies in its potentially multiple capabilities such as high sensitivity, high selectivity, low cost, and point-of-care (POC) applicability [22].
Figure 1.2 Application of nanomedicine within healthcare.
The application of nanotechnology in medical diagnostics can be categorized into two main groups: in vitro diagnostics and in vivo diagnostics.
• In Vitro Diagnostics
The ultimate aim of extracorporeal or in vitro diagnostics is the accurate detection of biological disease markers in the process of routine screening [23]. These diagnostic methods provide the necessary information for choosing the appropriate treatment regimen.
Traditional laboratory diagnostic techniques are highly expensive, labor-intensive, and time-consuming. These methods are based on sending the blood, tissue, or other body fluid samples to a laboratory for analysis which can cause sample deterioration [16]. These methods usually give inaccurate results and are unable to provide online and integrated monitoring. Therefore, different nanotechnology-based methods have been developed to provide the simultaneous and online determination of a broad range of biological markers using non-invasive techniques. Indeed, advances in the field of nanotechnology, material sciences, and the electronics industry have led to the development of a new generation of diagnostic devices that are smaller, faster, and cheaper. They do not require special skills and can provide accurate readings [24]. These devices are highly specific and require much smaller samples which reduce the invasiveness of the diagnostic tools and increase their effectiveness by providing detailed biological information (i.e., phenotypes, genotypes, and proteomes). Nanotechnology has enabled the development of high throughput diagnostic techniques, which can screen large numbers of samples for one disease or test one sample for numerous diseases, with POC applicability [3].
Nanotechnology-based in vitro diagnostic tools can be a single bio-sensor or an integrated device that contains an array of biosensors. Each biosensor consists of two main components: biorecognition element and transducer.
Figure 1.3 The main components of a biosensor.
The biorecognition element interacts with the analyte being tested, and the biological response is converted into an electrical signal by the transducer (Figure 1.3) [25]. The biorecognition element can be immobilized within nanoplatforms (e.g., nanoparticles or nanochannels) which enables the binding of a large number of receptors for capturing target analytes, thus providing highly sensitive detection [26].
The combination of nanotechnology and electronics has enabled the miniaturization of biosensors, allowing for highly integrated sensor arrays that can take different measurements in parallel from a single sample [27]. Moreover, microfluidic systems enable the incorporation of several complex preparation and analytical steps into ‘lab-on-a-chip’ diagnostic devices [28]. These devices can mix, process, and separate fluids for analysis and identification of various target analytes and measure tens to thousands of signals from one sample. Some of these devices have been developed to measure some part of the genome or proteome, which are called gene or protein chips [17, 18, 29]. These chips use DNA fragments or antibodies as their biorecognition element. Also, ‘cells-on-chips’, which use cells as their biorecognition element, are employed for the identification of pathogens and/or toxicology [30].
• In Vivo Diagnostics
The goal of in vivo diagnostics is to provide data from the patient instantaneously and track disease development and therapy continuously [31]. In general, in vivo diagnostics refer to imaging techniques and implantable devices.
Biomedical imaging has emerged from the blending of molecular biology with medical imaging, and it is the most relied-upon tool for the diagnosis of human diseases [26]. Biomedical imaging aims to create highly sensitive and reliable detection agents that can also deliver and monitor therapy. However, the detection of diseases at an earlier stage is the main aim [32].
Formerly, imaging techniques were performed only to detect changes in the appearance of tissues, which was possible when symptoms were relatively advanced. Afterward, the contrast agents enabled the identification and mapping of the disease locus. Today, the evolution of nanotechnology offers special characteristics that enable the development of new nanoparticles as novel contrast agents for more specific and sensitive imaging. This paved the way for the production of new medical imaging techniques with higher sensitivity and precision of recognition [33, 34]. Through the advancement of nanotechnology, both contrast agents and imaging methods are being effectively improved toward the end goals of detecting diseases early (eventually at the level of a single cell) and monitoring the effectiveness of the therapy [35]. Biomedical imaging techniques include several approaches such as optical bio-imaging (e.g., light scattering, absorption, luminescence, and nonlinear frequency mixing), magnetic resonance imaging (MRI), radio-isotope imaging, X-ray computed tomography (CT), and multimodal bio-imaging, which mostly depends on identifying tracers or contrast agents that have been introduced into the body to mark the disease site [26].
In addition, the miniaturizing of biosensors gives a chance for the development of implantable devices, another type of a novel in vivo diagnostic tool. These devices are an important class of biosensors because they can send continuous information about the levels of a target analyte or a specific biomedical parameter to a monitor outside of the body. These result in a big improvement in the living conditions of people who need permanent medical monitoring [36]. The developments in nanotechnology have a great potential to enhance the performance of these biosensors in the diagnosis, monitoring, management, and treatment of various diseases [37]. Wide research efforts have been initiated for the development of nanotechnology-based implantable biosensors used for continuous monitoring of various biologically relevant metabolites [38]. For example, implantable nano-biosensors are highly desirable for the management of diabetes. At present, diabetes management relies on data obtained from test strips using blood drawn from finger-pricking. This procedure is incapable of reflecting the overall trend and patterns associated with the daily blood glucose levels of the patient; therefore, implantable biosensors are highly desirable for diabetes management [39]. Also, intensive research is conducted on the development of implantable devices for monitoring other important biomedical analytes or signals [40], such as implantable biosensors for detecting electric signals and monitoring bio-analytes in the brain [41, 42].
1.4.2 Therapeutics
Nanotechnology and its usage in medicine have become an undeniable part of disease therapy nowadays. Conventional therapeutic techniques such as surgery, radiation, and chemotherapy are based on removing or killing diseased cells faster than healthy cells [43]. For instance, chemotherapy drugs are employed to kill cancer cells effectively, but in addition to tumor cells, these drugs kill healthy cells and cause several side effects such as nausea, hair loss, fatigue, and compromised immune function. The aim of nanomedicine is the development of therapy methods with minimally invasive treatment of the disease, directly and selectively at diseased tissues or cells.
Nanotechnology-based therapeutic techniques use nanoparticles and sophisticated approaches to either solely kill diseased cells or deliver active molecular and macromolecular agents to the specific tissue or cell. These novel techniques have several key advantages over conventional therapeutic techniques. First, nanoparticles and nano-carriers not only target specific organs or tissues in the body, but they also do so with cellular and subcellular specificity, which prevents drugs from interacting with normal cells, thus avoiding side effects. Second, the composition, size, shape, and surface properties of nanoparticles and nano-carriers can be perfectly tailored to protect drugs from being degraded in the body before they reach their target. Another major benefit is that a nano-carrier matrix can be designed to control the timing and distribution of drugs to the tissue which results in optimal and sustained drug action [44, 45].
As stated above, nanoparticles can be employed for either directly treating the disease or delivering the drug to a specific tissue or cell. These two applications of nanomaterials in disease therapy are described in the following sections.
• Drug Delivery
The initial reports of applying nanoparticles in therapy exclusively revolved around inert nanomaterials that were employed as drug carriers to improve therapeutic outcomes [46]. The drug delivery concept is based on the incorporation of a drug (e.g., chemotherapeutics, steroids, antibiotics, anesthetics, and painkillers) within carriers via absorption, adsorption, encapsulation, or conjugation to improve the bioavailability and pharmacokinetics of therapeutics.
Successful efforts have been made in the field of targeted drug delivery which enhanced efficacy, improved bioavailability, and reduced side effects of existing drug application methods. In these methods, nano-carriers are able to target a particular tissue (first order), a particular cell type (second order), or a particular organelle within a cell (third order) [26]. Also, targeting can be achieved by a passive or an active targeting mechanism.
The passive targeting mechanism is based on a process known as “enhanced permeability and retention” (EPR) which leads to enhanced delivery of circulating nanoparticles in tumor tissues. Nanoparticles with certain sizes and surface properties tend to accumulate in tumor tissue much more than they do in normal tissues. This property is known as the EPR effect and can reach a precision of second-order targeting at most.
The active targeting mechanism is based on the specific interaction between the surface-modified nanoparticles and receptors expressed on target cells or tissues, and it can achieve the precision of third-order targeting. In this method, nanoparticles must be modified with specific molecules that can bind particular cellular receptors. This enables nanoparticles to target cells expressing specific receptors. The combination of passive and active targeting mechanisms can further reduce the interaction of drug carriers with healthy tissues [16].
The nanoparticles involved in targeted drug delivery approaches are mostly liposomes and virosomes [47, 48], polymer-based nanoparticles [49, 50], and more recently, porous and carbon-based inorganic nanostructures [51–53]. These nanoparticles have the potential to (1) carry and exploit highly toxic, poorly soluble, and unstable drugs, (2) overcome the multidrug resistance (MDR) exhibited by cancerous and other diseased cells, and (3) release drugs in a controlled manner (i.e., sustained release, stimuli-sensitive release, and externally activated release).
• Drugs and Therapy
Nanoscale particles or molecules can act as “drugs” in the treatment of diseases due to their unique surface energy and physical properties [4]. Examples are fullerene or dendrimer-based drugs [54, 55]. Moreover, nanoformulation of hydrophobic drugs improves their dispersion, which maximizes drug efficacy, and thereby, improve health outcomes for patients [56]. These types of drugs have unique medical effects according to their structure which is different from traditional small-molecule drugs. For example, enzymatic degradation of these drugs can be largely prevented by appropriately tuning their size, shape, and surface properties [57].
Moreover, the advancement of nanotechnology in the biomedical domain has led to the development of novel therapies such as photodynamic therapy (PDT), photothermal therapy (PTT), magnetocytolytic therapy, and antimicrobial therapies [26, 58].
In PDT, the nanoparticles (photosensitizers) target diseased sites first, then it is followed by light irradiation. This energizes the photosensitizers and causes photodamage to the targeted cells. In PTT, the nanoparticle itself serves as a “drug.” In this technique, the metallic nanostructures, which absorb electromagnetic near-infrared (NIR) or infrared (IR) light, target diseased sites first. Light irradiation of these particles will then generate local heating which results in significant diseased cell death through necrosis. Magnetocytolytic therapy is based on the employment of magnetic nanoparticles and an external magnetic field. In this method, the magnetic nanoparticles are guided to the desired biological site using an external magnetic field. Then, these magnetic nanoparticles are activated using an external alternating current (AC)-magnetic field to generate local heating for disease-specific toxicity, also called “magnetically induced hyperthermia”. In antimicrobial therapies, metallic nanoparticles such as gold, silver, and platinum are employed to kill or inhibit the growth of microorganisms such as bacteria, fungi, or protozoans.
1.4.3 Theranostics
The term “theranostics” was coined in 1998 by John Funkhouser, the Chief Executive Officer of PharmaNetics, to describe a material that allows the combined diagnosis, treatment, and follow-up of disease [59]. Thus, theranostics (sometimes called theragnostic) can be considered as the combination of therapy and diagnosis in a single treatment, which has been enabled by extensive advances in nanotechnology (Figure 1.4).
A potential theranostic nanomaterial must include three main components: (1) a targeting moiety, (2) an imaging agent, and (3) a therapeutic agent. In theranostics strategies, the tissue of interest can be firstly targeted by the nanostructure using the targeting moiety. This specific nanostructure can carry both contrast and pharmacologically active agents, which can be employed for diagnostic (“find”) and therapeutic (“fight”) purposes simultaneously. Also, monitoring of tissue during treatment (“follow”) is possible by sequential imaging [60].
Figure 1.4 Theranostics can be considered as the combination of diagnosis, treatment, and follow-up with the ultimate aim of gaining personalized medicine.
The ultimate goal of the theranostic field is to identify the treatment strategy for individual patients, as opposed to adopting a ‘one-size-fits-all’ approach. This enables the switch from a “population treatment” approach to a “personalized medicine” approach [61]. Therefore, theranostic strategies must be able to, first, test patients for possible reactions to a new medication following their “molecular profile” and, second, tailor the personalized treatment based on the test results. The creative approaches developed for these classes of therapies include the combination of therapeutic strategies (e.g., chemotherapy, photodynamic, and radiation therapy) and one or more imaging functionalities (e.g., MRI contrast agents, fluorescent markers, and nuclear imaging agents). Personalized medicine-based treatments are of paramount importance to improve patient outcomes and health economics [62, 63].
Theranostic nanomedicine can be considered a relatively young field. Despite several promising theranostic approaches that have been developed, these techniques have not reached clinical trials. Extensive research is being conducted in this field to resolve some issues related to the application of these techniques, such as the difference between the optimum concentrations of therapeutic and imaging agents [61].
1.4.4 Regenerative Medicine
The NIH defines regenerative medicine as “the process of creating living, functional tissues to repair or replace tissue or organ function lost due to age, disease, damage, or congenital defects” [64]. According to this definition, regenerative medicine deals with the development of methods to regrow, repair, or replace damaged tissues and organs due to age, trauma, disease, or congenital defects. Active research in this field is focused on the generation of therapeutic stem cells, tissue engineering, and the production of artificial organs. Promising preclinical and clinical data to date support the successful application of regenerative medicine in replacing, treating, or healing different types of diseases and traumas, such as cardiovascular diseases and traumas, certain types of cancer, orthopedics issues, and dermal wounds [65].
The advent of nanotechnology has opened a new realm of advancement in the field of regenerative medicine. The application of nanotechnology has considerably accelerated the growth of regenerative medicine in recent years, and it appears to have great potential to revolutionize the regeneration of diseased tissues and organs and restore their function. In comparison to conventional regenerative techniques, the incorporation of nanotechnology allows better control over the physical and biological properties of a biomaterial [66, 67].
The active research in the field of regenerative nanomedicine is focused on (i) the development of cost-effective disease-modifying therapies for in situ tissue regeneration, (ii) the enhancement of the intrinsic regenerative capacity of the host by altering its environment, whether with cell injections or immune modulation, and (iii) the nanostructure optimization of surfaces and properties of prostheses (e.g., artificial joints) in order to produce materials that have a close connection to the body tissues, while avoiding side effects such as chronic inflammations or allergies. Extensive research has been conducted on the use of different types of nanoparticles (e.g., polymeric nanoparticles, inorganic nanoparticles, nanofibers, dendrimers, etc.) in the development of novel techniques for bone tissue, skin, cartilage, dental, and nerve regeneration [64].
1.5 Challenges
Although nanomedicine is an attractive field in life sciences with a significant potential to overcome biological barriers, there are challenges and limitations ahead of the development and commercialization of nanomedicine products. In order to successfully bring nanomedicine to patients, there are several obstacles identified.
One of the major challenges is crossing multiple biological barriers that the nano-formulated drug must overcome. The 3D complex of nanomedicines is made of different components having specific functions. This reveals the importance of full detection, characterization, and quantification of components as well as physicochemical and biological interactions between them. Consequently, a considerable number of analytical tests are required; some of them are sophisticated somehow. Moreover, not only is the technical aspect challenging in this topic, but the regulatory perspective should also be taken into consideration. Generally, the most important physicochemical properties of nanomedicine are composition, structure, size, surface properties, porosity, charge, and stability. The major challenge in characterizing nanomedicines is their variable properties, as well as the complexity of their stability and storage characterization. Some biodegradable materials, such as lipids and polymers, have been extensively used to develop nanomedicines; however, the biodegradable properties of nanomedicines can alter their properties during storage. So, it is vital to have well-defined and reproducible standards to assess the quality of biodegradable materials.
One other important issue is detecting and visualizing the in vivo bio-distribution of nano-carriers over time under clinically relevant conditions because the interaction of nanomedicine with biological fluids (e.g., blood serum) or biomolecules (e.g., proteins) can significantly alter the physicochemical properties and its function in biological systems. Although fluorescence or radiolabeling methods can obtain proper pictorial distribution of nanoparticle accumulation, quantifying mass balance information is still a challenge. Because the fluorescence and radiolabeling emitters are unstably conjugated to nanoparticles and can degrade easily, it may produce unreliable results if it traces the degraded moiety instead of the whole nanoparticle. Furthermore, the presence of fluorescence and radiolabeling emitters may lead to different properties compared to those using only the nanoparticle.
Manufacturing nanomedicines, as one of the key steps in developing nanomedicines, is successfully scaling up preclinical studies of nanomedicine products. The main issue, however, is controlling the stability of physicochemical properties on a batch-to-batch basis. Moreover, reproducibility can be achieved easier in small-scale processes than in large-scale production, which could lead to variation in physicochemical properties of different production batches.
Due to their complex 3D structure and specific arrangement of components, manufacturing nanomedicines is entirely different than that of a conventional pharmaceutical. Therefore, the components and their interactions have to be well understood to ensure large-scale manufacturing reproducibility. On the other hand, the high cost of the raw materials and expensive manufacturing of nanomedicines also illustrates the importance of pre-clinical studies.
Another substantial issue is the pharmacological and safety profiles of nanomedicines. It is vital that a produced nanomedicine achieves a favorable pharmacological profile, as even minuscule changes in composition and subtle deviations in the final product may lead to significant changes in its pharmacology. Also, the toxicity study of nanoparticles is vital due to their widespread application. Nevertheless, the nanomedicine toxicity evaluation is still difficult because conventional and classical drug toxicity assessment methods seem inadequate and inaccurate. Furthermore, a standard list of required tests needs to be provided so that standard criteria for nanomedicine products’ toxicity evaluation can emerge.
The Food and Drug Administration (FDA) and European Medicines Agency’s (EMA) approval for the commercialization of nanomedicine is necessary. Although several nanomedicine products have been approved so far, there are still no guidelines developed for them by the regulatory bodies. Due to that, the regulatory process is very time-consuming, and a high level of expertise is required. Because regulatory issues are crucial for developing such cutting-edge technology, detailed guidelines for the characterization and quality control of nanomedicine products have to be established.
Despite all the challenges and limitations, nanomedicine will forward to a new step and provide realistic and significant value to human medicine and healthcare.
1.6 Current Status and Future Perspectives
Research on nanomedicine has surged, as the number of publications has reached more than 5,400 articles in 2022 from less than 10 papers published in 2003 [68]. Also, from over 600 nanomedicines submitted to FDA from 1970 to 2019, more than 50% of them were submitted in recent decades [69]. Moreover, private and governmental funding programs for nanomedicine research and development are being increased to catalyze global activities and research in the field. According to worldwide business reports, more than 75% of the nanomedicine application area is captured by the drug delivery market, which is also the largest one [70]. The second generation of nanomedicine products is commercialized for cardiovascular infections, central nervous system (CNS) diseases, and cancer. The other application areas of nanomedicine are represented by products for imaging and diagnostics, tissue reconstruction, biosensors, and gene therapy.
Nanomedicine can present an important pathway for upgrading traditional pharmaceuticals. However, some new prospects and issues need to be taken into consideration carefully. These prospects are mainly opened up by nanomedicine being associated with risks and social and ethical questions. Although nanomedicine offers many huge opportunities, it still faces greater challenges compared to traditional drugs. Many nanotherapeutics have been able to get approval for clinical use so far and more drugs are being investigated in clinical trials; however, traditional drugs still dominate the market.
Approximately 80% of the newly manufactured nanomedicines approved by the FDA are liposomes, nanocrystals, emulsions, and micelles. Most of them are developed for the treatment of life-threatening diseases including tumors, immune disorders, and infections.
The future of nanomedicine utterly depends on the integration of intelligence, multifunctionality, and personalization. Intelligence can be described as designing intelligence-guided nanomaterials and intelligent intervening diseases by employing artificial intelligence (AI), deep learning approaches, and the development of nanorobots respectively. Multifunctionality is interpreted as the ability to integrate diagnosis, imaging, and therapeutic properties. Personalized therapy, as one of the key features of the future of nanomedicine, means customizing therapy according to the patient’s needs to not only provide the best response but also ensure better patient safety. Through this therapy, the patient is able to receive earlier diagnosis as well as optimal treatments while costs remain low. Considering all these, the future of nanomedicine is promising as it offers many advantages in disease diagnosis and therapy.
1.7 Conclusion
The ultimate goal of medical research is evident: curing diseases. Of course, nanomedicine is no exception. The steady development of nanomedicine, mainly due to its promising therapeutic efficacy and safety, is confirmed by the rapidly growing number of publications about it. Nevertheless, the applications of nanomedicine will have great impact on medicine in the coming years. These applications include early and rapid detection of diseases through simple, low-cost tests and high-accuracy imaging methods, introducing less invasive curing methods and optimizing existing ones, side effect-free medicines, significantly reduced aftercare costs, and diagnosis and therapy intermeshing. Nanotechnology has already made an important impact on clinical applications, which are expected to grow exponentially in the next few years.
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