Nanomedicine

A Systems Engineering Approach

Mingjun Zhang, Ning Xi

• Publisher: Jenny Stanford Publishing
• Year: 2019
• ISBN:
  9780429533662
• Edition: 1
• Topic: Technologie et ingénierie
• Subtopic: Science des matériaux

This book offers a fundamental and comprehensive overview of nanomedicine from a systems engineering perspective, making it the first book in the field of quantitative nanomedicine based on systems theory. The book starts by introducing the concept of nanomedicine and provides basic mathematical modeling techniques that can be used to model nanoscale biomedical and biological systems. It then demonstrates how this idea can be used to model and analyze the central dogma of molecular biology, tumor growth and the immune system. Broad applications of the idea are further illustrated by Bayesian networks, multiscale and multiparadigm modeling and AFM engineering.

Chapter One

Nanomedicine: Dynamic Integration of Nanotechnology with Biomedical Science

Ki-Bum Lee^*, Aniruddh Solanki, John D. Kim and Jongjin Jung

1.1 INTRODUCTION

The recent emergence of nanotechnology is setting high expectations in biological science and medicine, and many scientists now predict that nanotechnology will solve many key questions of biological systems that transpire at the nanoscale. Nanomedicine, broadly defined as the approach of science and engineering at the nanometer scale toward biomedical applications, has been drawing considerable attention in the area of nanotechnology. Given that the sizes of functional elements in biology are at the nanometer scale range, it is not surprising for nanomaterials to interact with biological systems at the molecular level. In addition, nanomaterials have novel electronic, optical, magnetic, and structural properties that cannot be obtained from either individual molecules or bulk materials. These unique features can be precisely tuned in order for scientists to explore biological phenomena in many ways. For instance, extensive studies have been done with chip-based or solution-based bio-assays, drug delivery, molecular imaging, disease diagnosis, and pharmaceutical screening.^{1, 2, 3, 4} In order to realize these applications, it is crucial to develop methods that investigate and control the binding properties of individual biomolecules at the fundamental nanometer level. This will require enormous time, effort, and interdisciplinary expertise of physical sciences associated with both biology and engineering. The overall goal of nanomedicine is to develop safer and more effective therapeutics as well as novel diagnostic tools. To date, nanotechnology has revolutionized biomedical science step by step not only by improving efficiency and accuracy of current diagnostic techniques, but also by extending scopes for the better understanding of diseases at the molecular level.^{5, 6, 7, 8} In this chapter, nanomaterials and their applications in biomedical research will be discussed.

1.2 DESIGNING NANOMATERIALS FOR BIOLOGY AND MEDICINE

One of the important technological aspects in nanomedicine lies in the ability to tune materials in a way that their spatial and temporal scales are compatible with biomolecules. That said, materials and devices fabricated at the nanometer scale can investigate and control the interactions between biomolecules and their counterparts at almost the single molecule level. This, in turn, indicates that nanomaterials and nanodevices can be fabricated to show high sensitivity, selectivity, and control properties, which usually cannot be achieved in bulk materials. The wide range of the scale of biointeractions is described in Fig. 1.

Figure 1. Scale of biomolecular interactions.

Given that one of the major goals of biology is to address the spatial-temporal interactions of biomolecules at the cellular or integrated systems level, the integration of nanotechnology in biomedicine would bring a breakthrough in current biomedical research efforts. In order to apply nanotechnology to biology and medicine, several conditions must be considered: (i) nanomaterials should be designed to interact with proteins and cells without perturbing their biological activities, (ii) nanomaterials should maintain their physical properties after the surface conjugation chemistry, and (iii) nanomaterials should be biocompatible and non-toxic.

In general, there are two approaches to build nanostructures or nanomaterials: “top-down” and “bottom-up” methods. Typically, the bottom-up approach utilizes self-assembly of one or more defined molecular building blocks to create higher-ordered functional entities. For the bottom-up approach, the physical and chemical criterion, such as pH, concentration, temperature, and intrinsic properties of building blocks, must be fulfilled. On the other hand, the top-down approach usually involves processes such as lithography, etching, and lift-off techniques to fabricate micro- and nanoscopic structured materials from bulk materials. In many cases, nanomedicine strategies have been derived from what was originally a conventional biomedical application, with a certain degree of modification to address some scientific questions or technical limitations. As far as the applications of nanostructures are concerned, we will examine two examples, nanoparticles and nanoarrays/biochips, which are heavily used in biomedical applications.

1.2.1 Inorganic Nanoparticles

Deoxyribonucleic acid (DNA), ribonucleic acid (RNA), peptides, and proteins are nanometer scale components that are the best examples of nanomaterials found in nature.^9,10 For example, DNA has a double-stranded helical structure with a diameter of 2 nm, RNA has a single strand structure with a diameter of 1 nm, and most of protein sizes are less than 15 nm. Likewise, the sizes of functional elements in biology are at the nanoscale level, which inevitably generate significant interests at the intersection between nanotechnology and biological science. Even though much progress in the life sciences has been achieved over the last few decades, biological and physiological phenomena still remain beyond our understanding, because the interactions between elementary biomolecules and other higher components, such as viruses, bacteria, and cells, are complex and delicate. Moreover, the interactions of two biocomponents start from the single molecule level, where the recognition sites lie in a nanoscale domain. Thus, studies of these biological components require not only an ability to handle the biological properties, but also to develop highly advanced tools or techniques to analyze the biological systems.^{11, 12, 13, 14}

Bioconjugated nanomaterials have recently been used as cellular labeling agents to study the biological phenomena at the nanometer level. With significant advancements in synthetic and modification methodologies, nanomaterials can be tuned to desired sizes, shapes, compositions, and properties.¹⁵ Inorganic nanoparticles are one of the most promising examples, since they can be synthesized easily in large quantities from various materials using relatively simple methods. Also, the dimensions of the nanoparticles can be tuned from one to a few hundred nanometers with monodispersed size distribution. Moreover, they can be made up of different metals, metal oxides, and semiconducting materials, whose compositions and sizes are listed in Table 1. Given many distinct properties, nanoparticles can be readily tailored with biomolecules via combined methodologies from bioorganic, bioinorganic, and surface chemistry.

Despite many significant advances in synthetic and surface modification methods, the fundamental development of bio-conjugation methods must first be achieved in order for the nanoparticles to be fully utilized. The bioconjugation strategies involve procedures for coupling biomolecules to nanomaterials, enabling the nanoparticles not only to be applied for clinical applications but also to ask and answer fundamental questions in cell biology. For the past few years, many methods have been developed for bio-labeled nanocomposites in various applications in cell biology: cell labeling, cell tracking,^{19, 20, 21, 22} and in vivo imaging.^23,24

Table 1. Selection of available nanoparticle compositions, sizes, and shapes.

Particle Composition	Particle Size (nm)
Metals
Au	2–250
Ag	1–80
Pt	1–20
Cu	1–50
Semiconductors
CdX (X = S, Se, Te)	1–20
ZnX (X = S, Se, Te)	1–20
TiO2	2–18
PbS	3–50
ZnO	1–30
GaAs, InP	1–15
Ge	6–30
Magnetic
Fe3O4	6–10
Various polymer compositions	20 nm to 500 μm

1.2.2 Coupling of Nanoparticles with Biomolecules

Interdisciplinary knowledge from molecular biology, bioorganic chemistry, bioinorganic chemistry, and surface chemistry must be employed to functionalize nanostructures with biomolecules. Although nanostructures can be synthesized from various materials using several methods, the coupli...

Table of contents

• Cover
• Half Title
• Title Page
• Copyright Page
• Table of Contents
• Preface
• List of Contributors
• Chapter 1 Nanomedicine: Dynamic Integration of Nanotechnology with Biomedical Science
• Chapter 2 Fundamental Mathematical Modeling Techniques for Nano Bio-Systems
• Chapter 3 A Mathematical Formulation of the Central Dogma of Molecular Biology
• Chapter 4 System Approach to Characterize Living Drosophila Embryos for Biomedical Investigations
• Chapter 5 Learning Signaling Pathway Structures
• Chapter 6 Computational Modeling of Tumor Biobarriers: Implications for Delivery of Nano-Based Therapeutics
• Chapter 7 Multiscale-Multiparadigm Modeling and Simulation of Nanometer Scale Systems and Processes for Nanomedical Applications
• Chapter 8 Game Theoretical Formulation of the Immune System and Inspiration for Controlled Drug Delivery Application
• Color Index
• Subject Index