Handbook of Materials for Nanomedicine

Metal-Based and Other Nanomaterials

Vladimir Torchilin

• Publisher: Jenny Stanford Publishing
• Year: 2020
• Print ISBN: 9789814800938
• eBook ISBN: 9781000067132
• Topic: Physical Sciences
• Subtopic: Biotechnology in Medicine

In the fast-developing field of nanomedicine, a broad variety of materials have been used for the development of advanced delivery systems for drugs, genes, and diagnostic agents. With the recent breakthroughs in the field, we are witnessing a new age of disease management, which is governed by precise regulation of dosage and delivery. This book presents the advances in the use of metal-based and other nanomaterials for medical imaging, diagnosis, theranostics, and drug delivery. It discusses silver, hybrid gold, and surface-modified magnetic nanoparticles, fluorescent quantum dots, lipid bubbles, and nanobubbles. It provides all available information about these materials and describes in detail their advantages and disadvantages and the areas where they could be utilized successfully. The text also covers topics such as improving bioactivity of poorly soluble actives, cellular and molecular toxicology of nanoparticles, and biofate of nanoemulsions.

Chapter 1

Hybrid Gold Nanoparticles

Alireza Gharatape^a and Roya Salehi^b

^a Department of Medical Nanotechnology,
School of Advanced Technologies in Medicine,
Tehran University of Medical Sciences, Tehran, Iran

^b Department of Medical Nanotechnology,
Faculty of Advanced Medical Science,
Tabriz University of Medical Sciences, Tabriz, Iran

[email protected], [email protected]

A journey of a thousand miles begins with a single step

—Lao Tzu (6th BC)

Hybrid gold nanoparticles have numerous applications in medical diagnosis and therapy. Many of these uses are associated with unique gold nanoparticles features. However, providing a comprehensive theranostic platform requires vast research, time, and cost. A large number of research teams focus on the application of hybrid gold nanoparticle. Interestingly, the significant results and the positive effects, which are observed on these hybrid nanomaterials, have led to some worldwide investigations. This chapter discusses hybrid gold nanoparticles and their synthesis, theranostic applications, and toxicity. In each section, along with the discussion of the mechanism and the scientific process, a number of research papers are discussed in detail.

1.1 Introduction

A few decades ago, no one could imagine nanometric particles which go into the body and explain what happened inside. In other words, it may seem like a science fiction that small particles can enter the body and cure diseases. After years of exploring the boundaries of science, scientists came up with a new multi-disciplinary scientific field called nanoscience and nanotechnology [1]. Nanotechnology deals with particles which have the small size between 1 to 100 nm (at least in one dimension) [2] that emerged in all of the scientific fields. Interestingly, nanotechnology plays a significant role currently. In medical research studies (diagnosis and therapy), many nanomaterials-based therapeutic and diagnostic systems have been developed recently [3, 4]. In therapeutics, nanomaterials have been used in synthetic drugs, modified drugs, and delivery systems to improve therapeutic efficacy. Furthermore, nanotechnology reduces costs and side effects of toxic chemical drugs by targeting therapy [4, 5, 6]. Besides, medical diagnostic equipment attained more precision and accuracy when nanotechnology was introduced in their fabrication.

In this regard, various types of nanomaterials (such as organic, inorganic, and synthetic materials) were used to improve and enhance diagnosis and therapy. Recently, dual-functional nanoparticles call to apply therapeutic and diagnostic effects [7, 8, 9, 10].

Inorganic nanomaterials have been studied extensively. Some of them demonstrated highly toxic effects which were appropriate for killing pathogenic organisms. In contrast, the toxic effect limited their application [11, 12]. Therefore, it is very important to choose a nanomaterial that normally does not have a toxic effect on the body.

Gold nanoparticles (GNPs) are metallic nanoparticles that have exclusive properties. Gold is an inert material which has several special properties. According to studies, GNPs have physical and chemical properties that adsorb or conjugate to different molecules such as (polymer, protein, peptide, ligand, aptamer, DNA, or RNA). Afterwards, the attached molecules transfer to the target site based on active or passive mechanisms. Eventually, the therapeutic effects of GNPs and transferred molecules demonstrate gradually [13, 14].

Hybrid nanomaterials are composed of two or more components that involve organic or inorganic nanomaterial with other molecules. These materials, which are composed of various molecules, provide unique properties and characteristics. The number of studies on hybrid nanomaterials is on rise [15, 16, 17, 18, 19]. Among hybrid nanomaterials, the application of hybrid gold nanoparticles (HGNPs) due to their special physical and chemical properties is consequently important. These nanomaterials are a good option in cancer therapy research, because they can detect some specific cells and then destroy them [15, 20].

This chapter provides a detailed discussion on HGNP synthesis methods (chemical and non-chemical), applications in imaging, targeting delivery, plasmonic photothermal and photodynamic therapy effects, and toxicity.

1.2 Gold Nanoparticle Synthesis

1.2.1 Chemical Synthesis Method

Chemical synthesis of GNPs is based on the chemical reducing agent which reacts with gold salts and produces GNPs. Various synthesis approaches have been developed in the past decades. From a general point of view, the synthesis methodology design depends on the type of application. In clinical usage and research studies, size, shape, morphology, and surface charge of GNPs are critical issues which are based on the type of application [21, 22, 23, 24, 25]. Generally, in the higher amount of reduction agent to salt, we can expect more intensive reaction and produce smaller particles [26, 27, 28]. In the following, several chemical synthesis methods are discussed in detail.

Tyagi et al. studied a citrate-based reduction method optimized at room temperature. They introduced a novel and easy method that did not require heat treatment. GNP synthesis with the Turkevich method involves several steps. In this method, Au³⁺ species were reduced to Au⁰. Eventually, with the accumulation of these atoms, the nanoparticles were formed. The size of nanoparticles depended on the number of accumulated atoms, even though the temperature has an important role in the mentioned method. They could prove the possibility of GNP synthesis at room temperature. In this method, particle size distribution was (11.7 ± 2.2 nm). A certain concentration of trisodium citrate dihydrate was mixed with gold (III) chloride and stirred at room temperature for up to 48 h. Eventually, pH was controlled by addition of the diluted solution of HCl or NaOH. The results demonstrated non-uniform shape and size of GNPs obtained in lower and higher than the optimal pH. Also, an optimal condition was obtained in a citrate to AuCl₃ ratio of 2:1 [29].

In another study, Ding et al. modified the Turkevich method to obtain smaller nanoparticles. They investigated the effect of latent heat on the synthesis of GNPs based on the Turkevich method. Briefly, latent heat is released or absorbed energy that is associated with a thermodynamic system at a constant temperature. The results show that the latent heat can cause around 3 nm reduction in the size of the GNPs. Accordingly, they succeeded in controlling the growth of nanoparticles and produced monodisperse GNPs for subsequent applications [30]. Schulz et al. tried to improve the Turkevich method by setting up an optimized protocol. GNPs with a diameter of around 8–12 nm and narrow size distribution were produced by pH adjustment with changing the citrate solution with citrate buffer. In addition, particle shape was improved and homogeneous GNPs were obtained by addition of ethylenediaminetetraacetic acid (EDTA) (Fig. 1.1) [31].

Shi et al. presented a new modification on the Turkevich method to reach smaller nanoparticles. In this procedure, they studied the citrate/gold salt ratio at the nanoscale. Generally, in this method, concentrated gold salt solution heated at 100°C was injected into a citrate-diluted solution which was heated at 100°C under vigorous stirring. After a few minutes, when the reaction occurred, the heat source was removed and the solution was allowed to cool down. They found this synthetic route produced nanoparticles more than conventional method [32].

Along with all the efforts made to improve the Turkevich method, Wuithschick et al. endeavoured to answer essential key questions about this synthetic route. An understanding of the general growth mechanism in the Turkevich method was the first question that they tried to answer. They found the Turkevich method follows the seed-mediated growth mechanism. In this procedure, the number of prepared particles at the end of the s...

Table of contents

• Cover
• Half Title
• Series Page
• Title Page
• Copyright Page
• Table of Contents
• 1. Hybrid Gold Nanoparticles
• 2. Gold Nanoparticles in Cancer Therapy
• 3. Silver Nanoparticles in Medicine
• 4. Surface-Modified Magnetic Nanoparticles in Medicine
• 5. Magnetic Nanoparticles in Theranostics
• 6. Activatable Fluorescent Quantum Dots
• 7. Lipid Bubbles and Ultrasound for Drug Delivery
• 8. Nanobubbles: State of the Art, Features, and the Future
• 9. Materials for Nanoemulsions and Their Influence on the Biofate
• 10. Nanocrystals: The Universal Formulation Principle to Improve the Bioactivity of Poorly Soluble Actives
• 11. Cellular and Molecular Toxicology of Nanoparticles
• Index