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Radiofrequency heating of gold nanoparticles for medical applications
KTH, School of Electrical Engineering and Computer Science (EECS), Electrical Engineering, Electromagnetic Engineering and Fusion Science.ORCID iD: 0000-0001-5396-141x
2025 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

In this thesis, the electromagnetic radiofrequency (RF) heating of gold nanoparticles (AuNPs) is investigated by means of analytical and numerical methods. The aim is to establish methods to identify model parameters for AuNP-mediated RF heating of biological tissue. These investigations can ultimately be used to assess the feasibility of a non-invasive and targeted method of cancer therapy by hyperthermia.

As a first step, an analytical model is developed, as a tool to study the absorption in a thin AuNP-treated cell substrate inserted in a waveguide. The interior of the waveguide is modeled as a continuous material composite with graded transition between the AuNP-treated layer and its surroundings. Exact analytical solutions for the fields, and the transmission and absorption parameters are obtained. The introduction of a scaling factor allows the calculation of the absorption within the AuNP-treated layer only, thus excluding losses in the surrounding material. Dispersive dielectric models describing the electromagnetic properties of relevant tissues are discussed and applied in numerical examples. The waveguide structure is numerically simulated in COMSOL Multiphysics, confirming the validity of analytical results.

The physical mechanisms that enable the heating of AuNPs by RF irradiation are not entirely understood. This thesis studies two proposed mechanisms and evaluates under what conditions they can amount to the required heating of the targeted tissue: electrophoretic oscillation and Joule heating. These effects are studied using electrostatic scattering theory.

RF Joule heating is found to be negligible in spherical AuNPs, but deemed possible in long nanowires. It is of particular interest to study how the presence of a thin dielectric shell affects the heating capacity in ellipsoidal AuNPs. In the context of the medical application, AuNPs are coated with functionalized ligands for tumor targeting. The Joule heating of coated AuNPs submerged in tissue is thus studied with respect to coating properties for AuNPs of all nanoscale-sized spheroidal shapes. The coating is found to strongly affect the overall AuNP heat absorption, and the effect is heavily dependent on the electromagnetic and spatial properties of the coating. The type of ligands to be used in practical applications should therefore be evaluated based on these properties, in addition to its targeting efficacy and biocompatibility.

Finally, the electrophoretic heating of AuNP suspensions is investigated. In the literature, this mechanism has been evaluated only for spherical AuNPs and mostly when they are submerged in aqueous solutions. Here, the electrophoretic heating is studied for any spheroidal shape in all nanoscale sizes. Heating is found to be strongest for spherical AuNPs a few nanometers in size dispersed in water, but significant heating is also observed in nanorods up to 40 nm in length and nanodisks with diameters up to 10 nm. However, the potency of the effect is strongly affected by the solvent. Due to the high viscosity in tissues, and in particular cancerous tissues, the study suggests that electrophoretic heating of AuNPs is negligible in these media. 

Abstract [sv]

I denna avhandling studeras elektromagnetisk radiofrekvensuppvärmning av guldnanopartiklar (AuNPs) med hjälp av analytiska och numeriska metoder. Syftet är att etablera metoder för att identifiera modellparametrar för AuNP-medierad radiofrekvensuppvärmning av biologisk vävnad. Dessa undersökningar kan i slutändan användas för att bedöma genomförbarheten av en icke-invasiv metod för cancerterapi genom riktad hypertermi.

Som ett första steg utvecklas en analytisk modell för att studera absorptionen i ett tunt AuNP-behandlat cellsubstrat insatt i en vågledare. Vågledaren med det insatta cellsubstratet modelleras som en kontinuerlig materialkomposit med graderad övergång mellan det AuNP-behandlade lagret och dess omgivning. Exakta analytiska lösningar för fälten, samt för transmissions- och absorptionsparametrar för vågledaren erhålls. Införandet av en skalningsfaktor möjliggör beräkning av absorptionen endast inom det AuNP-behandlade lagret, vilket utesluter förluster i det omgivande materialet. Dispersiva dielektriska modeller, som beskriver de elektromagnetiska egenskaperna hos relevanta vävnader, diskuteras och tillämpas i numeriska exempel. Vågledaren simuleras numeriskt i COMSOL Multiphysics, vilket bekräftar giltigheten av de analytiska resultaten.

De fysikaliska mekanismerna som möjliggör uppvärmning av AuNP genom radiofrekvent strålning är inte helt klarlagda. Denna avhandling studerar två föreslagna mekanismer, och utvärderar under vilka förhållanden de kan uppnå den erforderliga uppvärmningen: elektroforetisk oscillation och Joule-uppvärmning. Studeras med hjälp av elektrostatisk spridningsteori.

Radiofrekvent Joule-uppvärmning är försumbar i sfäriska AuNPs, men anses möjlig i långa nanotrådar. Det är av särskilt intresse att studera hur närvaron av ett tunt dielektriskt skal påverkar uppvärmningskapaciteten i ellipsoida AuNPs. Inom den tänkta medicinska tillämpningen är AuNPs belagda med funktionaliserade ligander för att kunna riktas mot en specifik tumör. Joule-uppvärmningen av belagda AuNPs i vävnad studeras således med avseende på beläggningsegenskaperna för AuNPs av alla sfäroida former på nanoskala. Det dielektriska skalet visar sig starkt påverka den totala AuNP-värmeabsorptionen, och effekten är starkt beroende av beläggningens elektromagnetiska och geometriska egenskaper. De ligander som ska användas i de praktiska tillämpningarna bör därför utvärderas baserat på dessa egenskaper, i tillägg till deras målinriktningsförmåga och biokompatibilitet.

Slutligen undersöks den elektroforetiska uppvärmningen av AuNP suspensioner. I litteraturen har denna mekanism främst utvärderats för sfäriska AuNPs i vattenlösningar. Här studeras den elektroforetiska uppvärmningen för en godtycklig sfäroid form på nanoskala. Uppvärmningen visar sig vara starkast för sfäriska AuNPs som är några nanometer stora och spridda i vatten, men betydande uppvärmning observeras också i nanostavar upp till 40 nm i längd och nanodiskar med diametrar upp till 10 nm. Den elektroforetiska effekten påverkas emellertid starkt av bakgrundslösningen. På grund av den höga viskositeten i vävnader, och i synnerhet i cancervävnader, antyder studien att elektroforetisk uppvärmning av AuNPs är försumbar i dessa medier.

Place, publisher, year, edition, pages
Stockholm: KTH Royal Institute of Technology, 2025. , p. 55
Series
TRITA-EECS-AVL ; 2025:5
Keywords [en]
gold nanoparticles, radiofrequency, hyperthermia, cancer therapy, scattering theory, waveguide theory
National Category
Other Electrical Engineering, Electronic Engineering, Information Engineering Nano Technology Atom and Molecular Physics and Optics
Research subject
Electrical Engineering
Identifiers
URN: urn:nbn:se:kth:diva-356769ISBN: 978-91-8106-146-8 (print)OAI: oai:DiVA.org:kth-356769DiVA, id: diva2:1917063
Public defence
2025-01-17, https://zoom.us/j/64235189553, H1, Teknikringen 33, Stockholm, 09:30 (English)
Opponent
Supervisors
Available from: 2024-11-29 Created: 2024-11-29 Last updated: 2024-12-04Bibliographically approved
List of papers
1. Analytical and Numerical Models for TE-Wave Absorption in a Graded-Index GNP-Treated Cell Substrate Inserted in a Waveguide
Open this publication in new window or tab >>Analytical and Numerical Models for TE-Wave Absorption in a Graded-Index GNP-Treated Cell Substrate Inserted in a Waveguide
2022 (English)In: Applied Sciences, E-ISSN 2076-3417, Vol. 12, no 14, p. 7097-, article id 7097Article in journal (Refereed) Published
Abstract [en]

In this paper, absorption phenomena in a hollow waveguide with an inserted graded dielectric layer are studied, for the case of transverse electric (TE) wave propagation. The waveguide model aims to be applicable to a study of a potential cancer treatment by heating of gold nanoparticles (GNPs) inside the cancer cells. In our previous work, general exact analytical fomulas for transmission, reflection, and absorption coefficients were derived. These fomulas are further developed here to be readily applicable to the calculation of the absorption coefficient within the inserted lossy layer only, quantifying the absorption in the GNP-fed cancer tissue. To this end, we define new exact analytic scale factors that eliminate unessential absorption in the surrounding lossy medium. In addition, a numerical model was developed using finite element method software. We compare the numerical results for power transmission, reflection and absorption coefficients to the corresponding results obtained from the new modified exact analytic fomulas. The study includes both a simple example of constant complex permittivities, and a more realistic example where a dispersive model of permittivity is used to describe human tissue and the electrophoretic motion of charged GNPs. The results of the numerical study with both non-dispersive and dispersive permittivities indicate an excellent agreement with the corresponding analytical results. Thus, the model provides a valuable analytical and numerical tool for future research on absorption phenomena in GNP-fed cancer tissue.

Place, publisher, year, edition, pages
MDPI AG, 2022
Keywords
waveguide, graded index, gold nanoparticles, optimal absorption, cancer treatment
National Category
Electrical Engineering, Electronic Engineering, Information Engineering Nano Technology
Identifiers
urn:nbn:se:kth:diva-316246 (URN)10.3390/app12147097 (DOI)000834488500001 ()2-s2.0-85137340298 (Scopus ID)
Note

QC 20220817

Available from: 2022-08-17 Created: 2022-08-17 Last updated: 2024-11-29Bibliographically approved
2. Parameter ranges and limitations on using gold nanoparticles for radio frequency-based hyperthermia treatment of cancer
Open this publication in new window or tab >>Parameter ranges and limitations on using gold nanoparticles for radio frequency-based hyperthermia treatment of cancer
2023 (English)In: 2023 35th General Assembly and Scientific Symposium of the International Union of Radio Science, URSI GASS 2023, Institute of Electrical and Electronics Engineers (IEEE) , 2023Conference paper, Published paper (Refereed)
Abstract [en]

In recent years, several researchers and research groups have proposed and studied a novel method of using gold nanoparticles (AuNPs) for radio frequency (RF) hyperthermia treatment of cancer. Such a method is occasionally described as a very promising new method for cancer treatment, without the side effects that are typical for other radiation treatments. It is well established that optical heating of AuNPs is caused by localized surface plasmon resonances. However, the physical mechanism behind RF heating of AuNP-fed biological tissue is a subject of some controversy. It is believed that the applied RF radiation drives the AuNPs into resonant oscillation, leading to relatively high dielectric losses, such that Joule and inductive heating is found to be negligible. In the present paper, we therefore perform an in-depth investigation of the parameter ranges and limitations that exist for the proposed methods of using AuNPs for RF hyperthermia treatment of cancer. Thereby, we show that a number of claims made so far about the potential of the proposed method are uncertain, and require further quantitative investigation.

Place, publisher, year, edition, pages
Institute of Electrical and Electronics Engineers (IEEE), 2023
National Category
Condensed Matter Physics
Identifiers
urn:nbn:se:kth:diva-339565 (URN)10.23919/URSIGASS57860.2023.10265576 (DOI)2-s2.0-85175186364 (Scopus ID)
Conference
35th General Assembly and Scientific Symposium of the International Union of Radio Science, URSI GASS 2023, Sapporo, Japan, Aug 19 2023 - Aug 26 2023
Note

Part of ISBN 9789463968096

QC 20231116

Available from: 2023-11-16 Created: 2023-11-16 Last updated: 2024-11-29Bibliographically approved
3. Radiofrequency absorption of coated ellipsoidal gold nanoparticles in human tissue
Open this publication in new window or tab >>Radiofrequency absorption of coated ellipsoidal gold nanoparticles in human tissue
2024 (English)In: Nanoscale Advances, E-ISSN 2516-0230, Vol. 6, no 7, p. 1880-1891Article in journal (Refereed) Published
Abstract [en]

Electromagnetic radiofrequency heating of gold nanoparticles for use in remote hyperthermia cancer treatment has seen rapidly growing interest in the last decade. While most of the focus has been on studying spherical nanoparticles, recent research suggests that using ellipsoidal particles can significantly increase the Joule heating. However, it is still unclear how the presence of ligands affects the electromagnetic absorption in this context. In the present paper, we study the effects of adding a surface coating to ellipsoidal gold nanoparticles, and investigate the change in absorption with respect to coating properties, particle aspect-ratio, and frequency. Both the case of a single nanoparticle and the case of a suspension of nanoparticles are studied. The introduction of a dielectric coating increases the absorption rate for particles with lower aspect ratios and at lower frequencies, potentially improving the flexibility of parameter configurations that can be used in treatment. A thermal analysis reveals that the absorption in the parameter space of lower aspect ratios translate to negligible differential temperature increase, even with the addition of coating. Furthermore, nanoparticles with very large aspect ratios (nanowires) generate less heat with coating compared to no coating. Thus, it is shown that the presence of coating and choice of aspect ratio, have significant impact on the absorption response and must be accounted for in the analysis of ligand-capped nanoparticles. The findings in the present paper provide a valuable tool to optimize the coated gold nanoparticle design parameters, in order to secure clinically useful differential heating.

Place, publisher, year, edition, pages
UK: Royal Society of Chemistry, 2024
Keywords
cancer therapy, hyperthermia, gold nanoparticles, radiofrequency, scattering theory
National Category
Nano Technology Biomaterials Science Other Electrical Engineering, Electronic Engineering, Information Engineering Atom and Molecular Physics and Optics
Research subject
Electrical Engineering
Identifiers
urn:nbn:se:kth:diva-356995 (URN)10.1039/d3na00876b (DOI)001153432900001 ()2-s2.0-85183500918 (Scopus ID)
Funder
Swedish Research Council, 2018-05001
Note

QC 20241129

Available from: 2024-11-28 Created: 2024-11-28 Last updated: 2024-11-29Bibliographically approved
4. Electrophoretic absorption of ellipsoidal gold nanoparticles – a parameter study
Open this publication in new window or tab >>Electrophoretic absorption of ellipsoidal gold nanoparticles – a parameter study
2024 (English)In: IEEE Journal of Electromagnetics, RF and Microwaves in Medicine and Biology, ISSN 2469-7249Article in journal (Refereed) Submitted
Abstract [en]

This paper investigates the RF electrophoretic response of ellipsoidal gold nanoparticles (AuNPs). Since the existing works generally consider the electrophoretic heating of spherical AuNPs, this work provides an important step towards understanding the behavior of ellipsoidal AuNPs. We first develop an analytical framework for modeling of electrophoretic response of ellipsoidal AuNPs. Thereafter, due to the lack of experimental studies of non-spherical electrophoretic RF heating of AuNPs, we validate our theory by comparison to the existing experimental results of spherical AuNPs as a special case, and estimate a few additional parameters not considered before. Then, parameter studies are performed on surface charge, friction constant, frequency, and ionic background, with respect to AuNP size and shape. Finally, we present new results for the electromagnetic absorption and heatrates of ellipsoidal AuNPs in human tissue. Our results from the tissue testing indicate a strong difference between aqueous media and realistic human tissues due to the major difference in the host medium viscosity. We demonstrate the electrophoresis’ strong dependency on the host medium’s viscosity, where we note that cancer tissue viscosity is more than a thousand times higher than that of water. We thereby confirm negative results for RF AuNP heating, indicated by our own previous study and two other previous studies. Our results provide important insights into the feasibility of RF AuNP heating in a medical context.

Keywords
cancer therapy, hyperthermia, gold nanoparticles, electrophoresis, radiofrequency, scattering theory
National Category
Nano Technology Other Electrical Engineering, Electronic Engineering, Information Engineering Atom and Molecular Physics and Optics
Research subject
Electrical Engineering
Identifiers
urn:nbn:se:kth:diva-357008 (URN)
Note

QC 20241217

Available from: 2024-11-29 Created: 2024-11-29 Last updated: 2024-12-17Bibliographically approved

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