Magnetic hyperthermia, Magnetic nanoparticles, Feedback control
Abstract
Hyperthermia therapy is a type of medical treatment in which body tissue is exposed to higher temperatures in an effort to treat cancer. Magnetic nano-particles are excellent for hyperthermia treatment. When a high frequency alternating magnetic field is applied, magnetic nanoparticles can increase the temperature which can then be used to kill cancer cells with minimum damage to the surrounding tissues. This Theses characterizes the physical properties such as size and magnetization, cell viability and heat generation capabilities against increasing magnetic field intensity. A feedback controller is also developed and its performance has been evaluated to monitor and control the temperature non-invasively using an Infrared camera. The developed feedback controller is then used for both in-vitro and in-vivo conditions in order to destroy the tumor. In-vitro studies are conducted with cancerous cell lines, HeLa and PC3, where cultured cells are heated with magnetic nanoparticles and cell death are characterized for different conditions. For in-vivo, PC3 xenograft tumor mice model was prepared and was treated by injecting magnetic nanoparticles directly into the tumor. These tumors were heated under alternating magnetic, increasing their temperature and resulting in cell death. A swarm of magnetic nanoparticles was manipulated inside the blood vessel of rat’s brain to show the possibility of targeted delivery of nanoparticles which can then be heated to kill cancer cells selectively. Keywords: Magnetic hyperthermia, Magnetic nanoparticles, Feedback control
Table Of Contents
1. Introduction 1 1.1. Cancer – Start, Growth, and Spreading 2 1.2. Conventional treatment methods and limitations 3 1.3. Hyperthermia – Heat energy to kill cancer 4 1.3.1. Principle of Hyperthermia 5 1.3.2. Classification of Hyperthermia 7 1.3.3. Nanotechnology for local hyperthermia 8 2. Magnetic hyperthermia therapy 11 2.1. Why hyperthermia with magnetic nanoparticles? 11 2.2. Heat generation mechanism and the effect of frequency and strength of the alternating magnetic field 12 2.3. Why superparamagnetic iron-oxide nanoparticles 14 2.4. Manipulation of magnetic nanoparticles 14 3. Characterization of magnetic nanoparticles physical parameters, heating and biocompatibility 18 3.1. Characterization of size 18 3.2. Characterization of magnetization of magnetic nanoparticles 20 3.3. Characterization of heat generation under alternating magnetic field 22 3.4. Characterization of biocompatibility of magnetic nanoparticles 24 3.4.1. Experiment preparation and conditions 24 3.4.2. Results and discussion 25 4. Closed-loop temperature controller 29 4.1. Design of the controller 29 4.1.1. Measurement 30 4.1.2. Proportional-Integral (PI) control 31 4.1.3. Actuator 33 4.1.4. Graphical User Interface (GUI) and Data logging 35 4.2. Performance Evaluation of the Controller 36 5. Hyperthermia treatments in-vitro and in-vivo 39 5.1. In-vitro hyperthermia treatment 39 5.1.1. Experiment preparation and conditions 39 5.1.2. Results and discussion 40 5.2. In-vivo hyperthermia treatment 44 5.2.1. Preparation of tumor model 44 5.2.2. Experimental conditions 46 5.2.3. Tumor volume measurement 46 5.2.4. Results and Discussion 48 6. Manipulation of magnetic nanoparticles swarm in blood vessel of rat’s brain 57 7. Conclusion 59 8. References 62