Nanotechnology in Cancer

Anshu Mathur

• Publisher: Elsevier
• Year: 2016
• ISBN:
  9780323390811
• Topic: Medicina
• Subtopic: Oncologia

Nanotechnology in Cancer covers current nanotechnology-based nanotherapeutics involving gold nanoparticles, colloids, gels, magnetic nanoparticles, radiofrequency, gene therapy, biological particles, and the intermolecular interactions associated with nanoparticle based cancer therapy in vivo.

Different cancer types and locations are considered alongside the corresponding treatment types, and the use of imaging technologies and animal models are also explored. Both scientific and clinical aspects are considered by authors coming from both fields, with the authors using their backgrounds from different disciplines to make the connection between cancer and effective drug delivery and therapeutic strategies.

• Authored by leaders from the scientific research and clinical communities who use their background from different disciplines to explore the connections between cancer and effective drug delivery and therapeutic strategies
• Brings together tumor biology, imaging technologies, nanomaterial platforms for drug delivery, therapeutic strategies, and reconstructive surgery
• Explores the clinical and regulatory challenges facing nanomedicine

Chapter 1

Gold nanoparticles for noninvasive radiofrequency cancer hyperthermia

S.J. Corr^1,2,3 and S.A. Curley^1,2, ¹Bayor College of Medicine, Houston, TX, United States, ²Rice University, Houston, TX, United States, ³University of Houston, Houston, TX, United States

Abstract

The use of gold nanoparticles as targeted, heating agents is currently being explored in the field of noninvasive radiofrequency cancer hyperthermia. This chapter gives an overview of the recent and current progress in this field, with a particular emphasis placed on gold nanoparticle heating mechanisms and their applications in in vitro and in vivo experimental models of hepatocellular carcinoma.

Keywords

Radiofrequency; gold nanoparticles; cancer; electric field; hyperthermia

Chapter Outline

Introduction 1

Brief Overview of Clinically Available Hyperthermia Systems 3

Nanoparticle-Mediated Cancer Hyperthermia 4

RF Interactions With AuNPs 7

Theoretical Frameworks for RF-Induced AuNP Heating 11

Joule Model 11

Classical and Quantum Electromagnetic Theory 11

Electrophoretic Model 12

Biological RF Activity of AuNPs In Vitro/In Vivo 13

Conclusion 16

References 16

Introduction

The use of gold nanoparticles (AuNPs) to deliver targeted, controlled hyperthermia is currently under investigation in the context of noninvasive radiofrequency (RF) cancer hyperthermia. It is thought that once these AuNPs have internalized within cancer cells, the exposure of the cells to an external, noninvasive (and nonionizing) RF electric field will initiate hyperthermia within those cancer cells only, leaving the neighboring healthy cells unaffected. A simplified overview of this process can be seen in Fig. 1.1.

Figure 1.1 Noninvasive RF system for cancer therapy. The patient is placed between the transmitting (Tx) and receiving (Rx) heads where a 13.56-MHz high-power electric field is generated. A breast tumor is shown in yellow (gray ellipsoid in print versions). As the tumor gets heated due to absorption of RF waves, the blood vessels dilate and become more permeable, increasing tumor blood flow and extravasation of macromolecules, chemotherapeutics, or nanoparticles from the vessels into the tumor tissue where they are internalized by cancer cells.

AuNPs have generally been the material of choice for this application over the last decade due to their well-established, facile synthesis protocols, which allow for a variety of shapes and sizes to be fashioned, as well as their bioinert nature, although this is still under debate. Due to their interesting electrical and conductivity properties, they were also deemed a perfect starting material as their interactions with electric fields could potentially elicit heating due to Joule heating mechanisms. As we will show however, this was not necessarily the case and indeed there has been intense speculation as to whether AuNPs are “hot or not” in the presence of an RF electric field.

Although the exact heating mechanisms of AuNPs are still under debate and are primarily studied in simplified aqueous solutions, there is an increasing amount of in vitro and in vivo evidence to suggest that AuNPs, especially those that are conjugated to antibodies and cancer chemotherapeutics such as C225 (Cetuximab) and gemcitabine (GCB), still have a place in the field of noninvasive RF cancer hyperthermia, and warrants further investigation.

Brief Overview of Clinically Available Hyperthermia Systems

The area of electric field cancer hyperthermia has been under investigation over the last century as a clinically relevant means of inducing noninvasive hyperthermia in patients with a variety of cancer types. A comprehensive review of the field can be found in the literature [1]. The treatment is based on the heat-inducing interactions of multifrequency electric field energy with biological tissues based on the nonzero dielectric properties of tissues, organs, and cancerous lesions (i.e., electrical energy is absorbed by the tissues and converted to heat, inducing hyperthermia).

Heating characteristics are dependent on the frequency of the electric field with most heating interactions occurring between 1 MHz and 1 GHz. As the frequency of the electric field increases, the penetration depths of the electric fields into the patient decrease. Hence, lower MHz frequencies are commonly used for the treatment of deep-seated tumors, while higher frequencies are often utilized for superficial tumor types.

There have been several system types investigated since the 1980s, each with their pros and cons, each with their varying levels of success with treating a variety of cancers. The first “main stream” commercially available clinical RF hyperthermia system was the Thermotron RF-8 (Yamamoto Vinita Co. Ltd., Japan) developed in the late 1970s/early 1980s. This system is an 8-MHz capacitively coupled system that utilizes water-cooled electrodes placed on opposite sides of the patient (i.e., parallel to each other with the intended treatment area “sandwiched” in-between). The body area between the two electrodes acts similar to the dielectric material found in electronic capacitors and is gradually heated as a function of power. Although this system is straightforward and easy to use, it does have inherent disadvantages such as high subcutaneous fat heating, which is alleviated somewhat by the use of a water-cooled “bolus”; as well as the instability of low-frequency RF field and its dependence on electrode size, location, and tissue parameters, which often result in “hot spot” formation. Several studies however have shown the effective use of this system (combined with and without radio- and chemotherapy) in the treatment of a variety of superficial and deep-seated cancer types, providing that the surface cooling and electrode configurations are properly managed [2].

Pyrexar Medical (formerly BSD Medical) has several systems available that include the BSD 500 and the BSD 2000 3D/MR. The BSD 500 is a self-contained treatment system for mobile applications using a fixed 915-MHz signal for treating superficial tumors located approximately 3–6 cm under the skin. On the other hand, the BSD 2000 3D/MR utilizes a 24-dipole antenna-phased array method (operating at 75–140 MHz) to accurately “steer” the electrical energy, and treatment area, within the patient at depths of up to 20 cm. This system can also be integrated into a magnetic resonance imaging (MRI) system to allow for MR thermometry—a means of visualizing the RF-induced temperature increases by analyzing the shift in proton resonance frequency, which is a function of temperature. The ability to measure internal RF-induced temperature changes is of critical importance for successful therapy: hence the MR integration. Clinical studies with this system have also seen some level of success. For example, in a recent randomized phase-3 multicenter study investigating the use of neoadjuvant chemotherapy alone or with regional hyperthermia for localized high-risk soft-tissue sarcoma (STS), it was demonstrated that the addition of hyperthermia increases the benefit of chemotherapy and is a new effective strategy for patients with high-risk STS, including STS with an abdominal or retroperitoneal location [3].

Another example is Celsius42+ GmbH who have developed a 13.56-MHz capacitively coupled system (Celcius TCS Hyperthermia System), which employs the use of two water-cooled electrodes (similar to the Thermotron RF-8 system) that effectively “sandwiched” the treated area between the two electrodes and allow the RF energy to be coupled into the patient. By combining chemotherapy or radiation therapy alongside the RF hyperthermia, they have shown interesting results (randomized phase III studies) in tumors of the head and neck, brain, breast, colon, rectum, and gynecological tumors. For further reference, other companies active in this area include OncoTherm, Andromedic, and Alba Hyperthermia.

The RF system currently under development in our laboratories is shown in Fig. 1.2. The device is based on a cascaded LC network whereby a high-power (100–1500 W) electric field operating at 13.56 MHz is transmitted from th...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• Contributors
• About the Authors
• Foreword
• Preface
• Introduction to Bio-Nanotechnology
• Chapter 1. Gold nanoparticles for noninvasive radiofrequency cancer hyperthermia
• Chapter 2. Silk fibroin nanoparticles and cancer therapy
• Chapter 3. Animal models in cancer nanotechnology
• Chapter 4. Surgical implications of surface texturing in breast implants
• Chapter 5. Nanoscale engineering of silk fibroin scaffold architecture to repair patient-specific cancer defects
• Chapter 6. Magnetic nanoparticles and cancer
• Chapter 7. Nanotechnology in neurosurgical oncology
• Chapter 8. Nanotechnologies for brain tumor therapy
• Index