Gold Nanoparticles for Cancer Photothermal Therapy

Rui Cao

School of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China

Keywords: Gold Nanoparticles, Photothermal Therapy, Cancer Therapy, Nanostructure.

Abstract: In recent years, there has been a great deal of interest in the new therapy of cancer treatment. Photothermal

therapy is one of the new ways to inhibit tumor formation. Many studies have confirmed gold nanoparticles

can absorb light at specific wavelengths, especially near-infrared light, through their unique optical

properties called localized surface plasmon resonance (LSPR) to achieve photothermal treatment of tumor

cells. Moreover, a large number of experiments have shown that gold nanoparticles with different structures

have different absorption spectra and LSPR peak position, which make them have different photothermal

efficiencies. In addition, gold nanoparticles modified by different functionalized compounds have better

biocompatibility and targeting ability, which greatly broadens the scope of its application in tumor

photothermal therapy and improves the therapeutic effect. In this paper, we conclude recent progress in gold

nanoparticles for cancer photothermal therapy. First, we introduce the optical properties of gold

nanoparticles and the principle of photothermal conversion. Then, the influence of different nanostructures

and functional modifications on the effect of photothermal treatment is discussed. Finally, we briefly

describe several common types of multifunctional gold nanoparticles, and introduce their basic principles

and functions. Due to the large amount of experimental data in relevant aspects, this paper mainly discusses

the research progress of gold nanoparticles in the field of photothermal therapy after 2015.

1 INTRODUCTION

Many studies have confirmed that gold nanoparticles

have unique optical properties. One of the most vital

optical properties of gold nanoparticles is the

collective coherent oscillation of their free

conduction band electrons, or the localized surface

plasmon resonance (LSPR) (Austin 2014). LSPR is

the coherent oscillation of the nanostructure’s

conduction band free electrons in resonance with the

incident electromagnetic field. Since the incident

light causes a high degree of polarization of the free

conduction band electrons, when gold nanoparticles

are placed in an external field, a displacement of

negative and positive charges will occur, that is, a

net charge difference is generated at the boundaries

of the nanoparticles (Ghosh 2007). Gold

nanoparticles can absorb/scatter incident light, and

photon confinement causes strong electromagnetic

fields and various optical phenomena on the metal

surface (Abadeer, 2016). This interaction strongly

depends on the composition, size, geometry,

https://orcid.org/0000-0001-9373-000X

dielectric environment and particle-particle

separation distance of nanoparticles (Petryayeva,

2011). So, the LSPR peak of the gold nanoparticles

can be changed by preparing nanoparticles with

different structures.

It is precisely because of the characteristics of

LSPR that gold nanoparticles can absorb light at a

specific resonance frequency, and the energy

absorbed can also be attenuated in the form of

radiation (such as optical scattering) and non-

radiation. Photothermal therapy uses the non-

radiative attenuation of energy, and uses the LSPR

effect to cause coherent oscillations of electrons in

the crystal lattice. In a very short time (femtosecond

scale), the electron pulses collide with the gold

crystal lattice, causing the electrons to generate

extremely high temperatures. Then, heat is

transferred to the outer surface of the gold

nanoparticle through the interaction between the

electron and the electron, the electron and the

phonon, and the phonon and the phonon, so that the

gold nanoparticle can heat the surrounding medium

(Austin, 2014).

Since tumors are more sensitive to temperature, a

short period of high temperature can effectively kill

Cao, R.

Gold Nanoparticles for Cancer Photothermal Therapy.

DOI: 10.5220/0011217400003443

In Proceedings of the 4th International Conference on Biomedical Engineering and Bioinformatics (ICBEB 2022), pages 471-477

ISBN: 978-989-758-595-1

471

cancer cells around the gold nanoparticles and

induce their apoptosis. Also, by changing the

structure of gold nanoparticles, the LSPR can be

excited at near-infrared light, and near-infrared light

has a stronger penetration of physiological

structures, which can better activate the

nanoparticles in the body.

Gold nanoparticles can also be functionalized

with surface modification to improve their targeting

ability and specificity, so that they can be better

enriched at the tumor site, thereby improving the

effect of photothermal treatment.

Therefore, this review focuses on the impact of

the structure and functionalization of gold

nanoparticles on the effect of photothermal therapy.

By summarizing the photothermal conversion

efficiency of gold nanoparticles of various

structures, we try to find the most advantageous

structure, hoping to provide structural suggestions

for the future research of gold nanoparticle

photothermal therapy.

2 CHARACTERIZATION OF

GOLD NANOPARTICLE

A large number of studies have shown that in

addition to increasing the heat output by changing

the incident light power, the shape, size and surface

characteristics of the gold nanoparticles can also be

optimized to adjust the LSPR peak and photothermal

conversion efficiency (Singh, 2018). Considering the

penetration depth and safety of light in physiological

tissues, the LSPR peak of gold nanoparticles used in

most photothermal treatments is in the first (650-850

nm) or second (950-1350 nm) near-infrared window

(Riley, 2017). Therefore, the structure of the

nanoparticles needs to be adjusted to maximize the

absorption of laser light in this window.

Studies have shown that small size (<8nm) gold

nanoparticle is little cytotoxicity, which can be

filtered in the kidneys, whereas larger nanoparticles

size (> 10nm) likely to remain in the body cannot be

discharged, which aggregates in the liver and

kidneys, causing damage to cells (Vines, 2019).

However, small-sized gold nanoparticles are easily

excreted and are not easy to aggregate in tumor cells,

and oversized nanoparticles are not easy to pass

through the blood vessel wall into tumor cells. Both

of these will affect the killing effect of photothermal

therapy on tumor cells. Therefore, it is necessary to

control the size of gold nanoparticles to find the best

effect.

At present, common gold nanoparticle shapes

include gold nanospheres, gold nanorods, gold

nanoshells, gold nanostars, and gold nanocages.

These shapes have different light absorption cross-

section and LSPR peaks, so as to have a different

wavelength of light absorption and photothermal

conversion efficiency. In addition, the different

shapes mean that the surface properties of these gold

nanoparticles are different, which affects their ability

to adsorb to tumor cells or the difficulty of being

swallowed by them. These can be changed by

improving the structure of nanoparticles, thereby

ultimately increasing their enrichment at the tumor

site, reducing damage to the surrounding normal

tissues, and effectively improving the efficiency of

photothermal conversion (Guo, 2017).

Table 1: Photothermal properties of some gold nanoparticles with different shapes.

Gold nanoparticle

shape

Size(nm)

LSPR peak

position(nm)

Laser

Photothermal

conversion

efficiency

References

nanorods

Au-TEMPO NRs 39.2(aspect ratio 3.85) 785 808nm,1.13 W/cm2 - (Xia 2018)

AuNR-MEND 68±18.3 788 750~900nm,1.0W/cm2 -

(Paraiso

2017)

Bi2S3-Au NRs 271±19.5 - 808nm,0.75W/cm2 51.06%

(Cheng

2018)

AuNR-Glu 134.4(±6.2)×23.9(±1.8) 1070 1064nm,1.0W/cm2 43.12% (Li 2018)

GNRS-HA-FA-DOX 70.9±1.4 779 808nm,2.0W/cm2 - (Xu 2017)

GNR-HA-

ALA/Cy7.5-HER2

55.1(±1.7)×14.1(±1.1) 800 808nm,2.0W/cm2 - (Xu 2019)

nanoshells

Tf-GNRS 205.8(±13.1)×112.0(±4.8) 808 808nm,8.0W/cm2 17.70%

(Zhao

2017)

ICBEB 2022 - The International Conference on Biomedical Engineering and Bioinformatics

472

ICG−Au@BSA−Gd 151.1 ~850 808nm,1.5W/cm2 21.77% (You 2017)

nanocages

CM-EM-

GNCS@DOX

~60 790 808nm,0.5W/cm2 - (Sun 2020)

GSNCs 35±3 532 808nm,1.0W/cm2 - (Qin 2019)

EpCam–RP AuNs 69.7 750 808nm,2.5W/cm2 - (Zhu 2018)

nanospheres

GSH-AuNPs 3 515 800nm,2.5W/cm2 90%

(Barram

2021)

AuNP@Mo4Zol2Mn 47.6±7.8 528 680nm,1.7W/cm2 59±5%

(Tomane

2021)

dAuNPs 20.5±1.9 700~900 808nm,1.0W/cm2 78.80%

(Cheng

2017)

BSA-AuNPs ~4 540 800nm,0.5W/cm2 -

(Jawad

2018)

LACP 101.2±5.6 - 514nm,24mW/cm2 -

(Wang

2018)

nanostars

AuNSs@PDA-PEG 114 806 808nm,0~2.0W/cm2 - (Li 2019)

rGADA 51.3 - 808nm,0.1W/cm2 66.30% (Jia 2020)

There have been many studies on the influence

of the structure and size of gold nanoparticles on the

efficiency of photothermal conversion. The structure

and photothermal conversion efficiency of them are

shown in the table, and there is a big difference

between them. (Table 1) It is noted that the LSPR

peak positions of the gold nanoparticles with the

same shape are almost the same. Most of them will

have a certain blue shift or red shift due to the

difference in functional modification and size.

However, a few of them have different structures

due to special synthesis or processing methods,

which makes them have a big difference in optical

properties from other nanoparticles of the same type

of structure. The positions of the LSPR peaks of the

gold nanoparticles prepared into different shapes are

quite different, since the different surface

characteristics caused by their shapes leads to the

differences of the electromagnetic wave wavelengths

which cause surface ion resonance. However, the

photothermal conversion efficiency is not

necessarily related to the difference in these

structures or surface modifications. Since these

efficiencies are not measured in a physiological

environment, the photothermal conversion efficiency

of gold nanoparticles in vivo may be affected by

many factors and changes. It is noted that many

reports indicate that gold nanoparticles may

aggregate in a physiological environment, and

changing the intensity of laser irradiation and the

concentration of the gold nanoparticle solution will

also affect the photothermal conversion, which

makes it impossible to compare the efficiencies

measured in different experiments. In addition, some

materials used for functionalization or surface

modification of gold nanoparticles will also affect

their light/heat conductivity, thereby affecting the

efficiency of photothermal conversion. For example,

gold nanorods functionalized based on hyaluronic

acid are modified differently to have different

photothermal treatment effects. Xu. W et al (Xu,

2017). In vitro experiments, the total apoptotic rate

of MCF-7 cells treated with hyaluronic acid

functionalized gold nanorods modified by folic acid

(GNRS-HA-FA-DOX,66.00%) was much higher

than that of those that were not modified by folic

acid (GNRS-HA-DOX,37.17%). Therefore, it is

impossible to conclude which shape or

functionalization of gold nanoparticles has the best

photothermal conversion efficiency. In view of this,

it is considered that it is useful to calculate the

photothermal conversion efficiency when improving

the photothermal treatment effect of a certain gold

nanoparticle, which can reflect its heating efficiency

in the body and its killing effect on cancer cells to a

certain extent.

Although the properties of gold nanoparticles

with the same structure will be very different, they

also have many commonalities. For example, due to

its unique shape, gold nanorods have been a popular

structural research direction since they were first

synthesized. As a slender anisotropic shape, it has

two LSPR peak positions, including transverse

plasmon resonance (TSPR) on the short axis (mostly

Gold Nanoparticles for Cancer Photothermal Therapy

473

in the visible region) and longitudinal plasmon

resonance (LSPR) on the long axis (mostly in the

near-infrared region) (Elahi 2018). In addition, the

longitudinal absorption peak is affected by the

aspect ratio, which shows that the peak position

redshifts as the aspect ratio increases (Brolossy

2008). Thus, because of its unique optical and

physicochemical properties, the gold nanorods are

widely used in photothermal therapy. As one of the

first studied structures, gold nanospheres have

gained popularity due to their small size and ease of

synthesis. The position of the LSPR peak of gold

nanospheres is mainly affected by its size. The size

increases from 1 to 100 nm, and the relative

absorption peak of the size is 500 to 550 nm (Elahi

2018). Due to its small size, it can be coupled or

modified with many ligands, effectively improving

its photothermal performance.

3 MULTIFUNCTIONAL GOLD

NANOPARTICLES

In many studies, gold nanoparticles for photothermal

therapy are not single functional. Many of them will

be combined with other popular anti-cancer

detection methods or treatment methods, including

photodynamic therapy, tumor imaging, biosensing

and drug delivery.

The common multifunctional combination of

gold nanoparticles is photodynamic therapy and

photothermal therapy, both of which use light

absorption to kill tumor cells. Effective fluorescence

quenching and local surface plasmon resonance

(LSPR) absorption, easy to combine with

mercaptans, disulfides and amines, gold binding

facilitates intracellular penetration is also the reason

why gold nanoparticles can be used for

photodynamic therapy. The difference is that

photodynamic therapy is a biochemical action

induced by a photochemical reaction, which uses

light, photosensitizers, and oxygen from tissues.

During the process, the photosensitizer needs to be

injected into the tumor site. Because the half-life of

the photosensitizer administered systemically or

locally is different in each tissue, the concentration

of the photosensitizer in the tumor tissue is

significantly higher than that in the normal tissue

after a period of time. Selective retention, under the

action of excitation light of a specific wavelength,

and in the presence of molecular oxygen, singlet

oxygen and other reactive oxygen species (ROS) are

produced, leading to tumor cell necrosis and

apoptosis. Secondly, PDT can also destroy the

capillaries in tumor tissues, causing ischemia and

hypoxia, leading to cell death. Finally, PDT can

induce a variety of immune cells to rapidly infiltrate

the tumor, activate the complement system, and

promote the production and release of a variety of

cytokines/chemical factors, and finally initiate the

body's immune response to kill the tumor (Singh,

2018, Elahi, 2018). Unlike PTT, which does not rely

on oxygen, PDT is completely dependent on the

availability of tissue oxygen. Therefore,

photodynamic therapy does not affect the

photothermal treatment effect of gold nanoparticles

itself. For example, based on the new photosensitizer

BPS, combined with the plasma photothermal agent

Au nanoparticles and the targeting agent Fe3O4

nanoparticles, the multifunctional

BPS@Au@Fe3O4 was successfully prepared

through a simple, gentle and reproducible method.

The final prepared composite material has a wide

light absorption band and photodegradable

properties. Yang, D et al (Yang, 2017).

Experimental results show that BPS@Au@Fe3O4

nanoparticles have a high degree of biocompatibility,

and low-power near-infrared laser-mediated

synergistic photothermal and photodynamic therapy

shows excellent tumor suppression effects. At the

same time, the combination of photodynamic effect,

photothermal effect and magnetic resonance imaging

is helpful for comprehensive and integrated

treatment of tumor sites and improve the effect of

cancer treatment.

The most common combination is to use gold

nanoparticles as a carrier, not only for photothermal

therapy, but also as a carrier for other drugs or

ingredients, to play a role in drug delivery. The

coupling of gold nanoparticles and drug molecules

plays an important role in the treatment of

intracellular diseases. Their unique physiological

properties can promote the delivery of drugs into

cells, thereby improving the efficacy of drugs.

Antibiotics or other drug molecules can be directly

coupled to gold nanoparticles through ionic or

covalent bonds or physical absorption. At the same

time, because AuNPs have unique optical, physical

and chemical properties, biocompatibility, functional

flexibility, adjustable monomolecular membrane,

controllable dispersibility, high drug loading density

surface area, stability and non-toxicity, etc. Make it

an effective nanocarrier in the drug delivery system

(DDSS). These effective nanocarriers can transfer

various drugs, such as peptides, proteins, plasmid

DNA (PDNAs), small interfering RNAs (SiRNAs)

and chemotherapeutic drugs. Gold nanoparticle

ICBEB 2022 - The International Conference on Biomedical Engineering and Bioinformatics

474

carriers can be used to control drug delivery and

release methods, such as the use of external stimuli

(such as light) or internal stimuli. Therefore, it can

effectively combine chemotherapy and photothermal

therapy, while using physical and biochemical

methods to kill tumors (Elahi, 2018, Kong, 2017).

For example, the gold nanocage wrapped in red

blood cell membrane is used as a carrier to load the

anti-tumor drug paclitaxel (PTX) for targeted

photothermal and chemotherapy for cancer. Zhu, D

et al (Zhu, 2018). The results show that EpCam-

RPAuNs nanoparticles have better targeting ability

to 4T1 cells than unmodified nanoparticles. The high

temperature generated by AUNS under 808 nm near-

infrared radiation has a dual effect. First, the

increase in temperature promotes the release of PTX

by destroying red blood cell vesicles. Second, as a

photothermal treatment method, it directly uses

hyperthermia to kill cancer cells. In addition,

overheated AuNs will cause a large number of

cancer cell deaths, which will greatly reduce the

viability of 4T1 cells. The combination of the two

results in better tumor treatment efficiency. For

another example, a cancer cell-erythrocyte hybrid

coated doxorubicin (DOX) gold-loaded nanocage

(CM-EM-GNCs@DOX) is used for the combined

treatment of breast cancer with

photothermal/radiotherapy/chemotherapy. Sun, M et

al (Sun 2020). CM-EM-GNCs@DOX has good

photothermal conversion effect and near-infrared

response drug release behavior. Compared with

naked GNCs, CM-EM-GNCs@DOX has high

homology targeting to MCF-7 cells, and because it

retains the characteristics of cancer cell membranes

and red blood cell membranes, it has a good immune

escape ability. Under near-infrared irradiation, CM-

EM-GNCs@DOX exhibits a high photothermal

effect, which not only breaks CM-EM-GNCs@DOX,

releases DOX for precise and controllable

chemotherapy, and is enhanced by photothermal

therapy Received chemotherapy/radiotherapy.

In addition to the above two common

multifunctional gold nanoparticles combined with

photothermal therapy, some gold nanoparticles are

designed with both sensing and imaging in mind,

integrating tumor inspection and treatment, thereby

improving cancer treatment efficiency. Due to the

LSPR effect, gold nanoparticles show strongly

enhanced radiation properties (ie, light absorption,

scattering, and fluorescence), making them a

potential multi-modal imaging agent. The currently

commonly used iodinated aromatic compound

contrast agents have high water solubility and low

toxicity, but the blood circulation time is very short,

and they will be excreted through the kidneys soon.

Compared with ordinary reagents, gold

nanoparticles can stay in the blood vessel for a

longer period of time while taking into account the

non-toxic and harmless safety. Therefore, it can be

used as a contrast agent for tumor imaging at the

same time as photothermal therapy (Elahi, 2018,

Dreaden, 2012). The rich chemical and physical

properties of gold nanoparticles make them also

useful for biosensing. Sensors for different purposes

take advantage of the different characteristics of

AuNPs. For example, fluorescence-based sensors

utilize the fluorescence quenching properties of

AuNPs, surface plasmon resonance sensors based on

the optical properties of AuNPs, and biological

barcode analysis based on strong binding affinity to

thiols and visible color changes due to aggregation

of gold nanoparticles (Elahi, 2018). These sensors

that use the properties of gold nanoparticles can be

combined with photothermal therapy to perform

treatment while detecting.

4 CONCLUSION AND

PERSPECTIVES

In conclusion, we summarized the basic principles

of the photothermal properties of gold nanoparticles,

and analyzed the latest research on nanoparticles of

various structures to find out how the structure and

functionalization affect the photothermal conversion

efficiency, such as changing the effective light

absorption area, aspect ratio or size. Besides, we

have confirmed the commonalities of nanoparticles

with the same structure, which allows us to use the

advantages of gold nanoparticles with different

structures to solve different photothermal treatment

needs.

In recent years, the technology of synthesis and

functional modification of gold nanoparticles has

developed rapidly, leading to the production of

many gold nanoparticles with unique properties and

different structures. And because of the antibacterial,

anti-oxidant and easy modification properties of

gold itself, taking advantage of these characteristics

and functionalizing nanoparticles can make it more

widely used in the field of photothermal therapy. In

future research work, more attention should be paid

to the targeting properties of gold nanoparticles so

that they can be more actively targeted to specific

sites. Moreover, it is necessary to continue to

improve the structure or surface modification to

reduce its cytotoxicity and avoid its excessive

Gold Nanoparticles for Cancer Photothermal Therapy

475

discharge from the body or long-term retention in

the body. Last but not least, it is also vital to study

gold nanoparticles that combine photothermal

therapy with other tumor treatment methods, such as

drug delivery or optical imaging, so as to achieve a

comprehensive cancer treatment that integrates

diagnosis and treatment.

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