1. Introduction
Recently, ultraviolet exposure has increased due to increased outdoor activities as a result of global economic development. Accordingly, the incidence of skin cancer is increasing annually [
1,
2]. Skin cancer can be primarily classified into squamous cell carcinoma, basal cell carcinoma, and malignant melanoma, and the treatment of these skin cancers is performed using various methods such as chemotherapy, cryotherapy, and incision [
3,
4,
5]. These therapy methods, however, pose various negative effects [
6,
7,
8]. In particular, surgery via incision causes bleeding and possible secondary infection [
9,
10].
An alternative treatment (i.e., photothermal therapy) is garnering attention as a method that can alleviate these adverse effects [
11,
12]. Photothermal therapy is a treatment method that uses the photothermal effect, a phenomenon in which light energy is converted into thermal energy when light energy is irradiated onto a medium, to induce the death of tumor tissues by increasing the temperature of the target tumor tissue [
13,
14]. This treatment method affords quick recovery and minimal risk of subsequent infection [
15,
16]. Photothermal therapy primarily supplies heat to biological tissues via laser, thereby affording the easy control of the heating range and intensity [
17,
18]. When a visible ray laser is used (among lasers of various wavelengths), a significant amount of light absorption occurs not only in the target tumor tissue, but also in normal tissues. Hence, laser in the near-infrared region, which involves a low light-absorption coefficient in biological tissues, is applied in photothermal therapy [
19]. However, because the tumor tissue has a low light absorption rate with respect to laser in the near-infrared region, a light absorption enhancer is injected into the tumor tissue to increase the light absorption rate of the tumor tissue to perform treatment. This causes a temperature increase in only the tumor tissue, enabling selective treatment [
20]. Among the various light absorption enhancers, gold nanoparticles (AuNPs) are widely used because they are harmless to the human body and afford high surface workability [
21,
22,
23]. AuNPs reach the tumor in various ways such as direct administration and intravenous injection, and are injected into the tumor through a process such as endocytosis and used for treatment [
24,
25,
26].
Biological tissues including tumor tissues cause various types of death depending on temperature [
27,
28]. Apoptosis occurs between 43 °C and 50 °C, and is a form of self-death that does not affect the surroundings. Necrosis, in contrast, occurs at temperatures of 50 °C or above; it poses the risk of cancer cell metastasis and recurrence as it affects adjacent tissues when the tissue dies. Accordingly, the temperature range corresponding to apoptosis should be maintained to prevent necrosis. In photothermal therapy, treatment is performed by controlling the appropriate intensity of the heat source, injection amount of AuNPs, and type of AuNPs to minimize thermal damage to surrounding normal tissues while maintaining a temperature band corresponding to apoptosis [
29].
Based on these factors, various studies regarding photothermal therapy are being conducted. Nam et al. [
30] conducted an experimental study pertaining to photothermal therapy combined with chemotherapy. Polydopamine-coated spike-shaped AuNPs with excellent photothermal stability and optical efficiency were developed to enable photothermal therapy; consequently, successful treatment for 85% of CT26 colon carcinoma cases was confirmed. In addition, the therapeutic efficacy of TC-1 submucosa-lung metastasis was confirmed. Mackey et al. [
31] conducted a study regarding photothermal therapy using rod-type AuNPs. The study was conducted both theoretically and in vitro, and information pertaining to the shapes of three sizes of gold nanorods that afforded the optimal therapeutic effect was obtained. Finally, it was demonstrated that gold nanorods with a length of 28 nm and a diameter of 8 nm were the most effective light absorption enhancers. Broek et al. [
32] conducted an experimental study regarding photothermal therapy using branched AuNPs. In this study, branched AuNPs were biofunctionalized with nanobodies of heavy chain-only antibodies and bound to HER2 antigen expressed in both breast and ovarian cancer cells. As a result of the treatment, it was confirmed that the tumor died when 690 nm continuous wave (CW) laser was irradiated with an intensity of 38 W/cm
2 for 5 min, and that the tumor was killed only under an optical density of 4 or higher when the corresponding AuNP was used. ** et al. [
33] developed new photothermal agents (PTAs) to improve the low photothermal conversion efficiency (PCE) of conventional PTAs. PCE is facilitated by the -CF3 moiety included in the meso-position of the BODIPY scaffold in the PTAs because the free rotation of -CF3 provides a pathway for efficient non-radiative decay. In addition, it was confirmed that the barrier-free rotation of -CF3 continued even when tfm-BDP was encapsulated with polymer nanoparticles. Excellent therapeutic effects were confirmed in both in vitro and in vivo experiments, and mouse experiments confirmed that tfm-BDPNP was efficiently accumulated in the tumor area and completely resected tumor tissue when near-infrared lasers of 0.3 W/cm
2, 808 nm were used.
In summary, studies regarding photothermal therapy under various conditions have been conducted both experimentally and theoretically. However, treatment trends based on different types of AuNPs and laser irradiation conditions could not be determined, and studies suggesting optimal treatment conditions quantitatively when considering various AuNP concentrations and other conditions at the same time are insufficient. In addition, although photothermal therapy induces cell death through temperature increase due to the photothermal effect, studies pertaining to heat transfer are insufficient. Therefore, in this study, a numerical study of photothermal therapy based on heat transfer theory was conducted for actual skin layers including squamous cell carcinoma. The temperature distribution in tumor and normal tissues based on various AuNPs shapes, laser intensities, and volume fractions of injected AuNPs was obtained. In addition, the optimal treatment effect was proposed by quantitatively confirming conditions that maximize the apoptosis of tumor tissues while minimizing thermal damage to surrounding normal tissues, which is the main purpose of photothermal therapy based on the apoptotic variable proposed by Kim et al. [
34].
4. Conclusions
In this study, a numerical study based on heat transfer theory was performed to investigate photothermal therapy using AuNPs on an actual skin layer containing squamous cell carcinoma. The temperature distribution inside the biological tissue was calculated using the Pennes bioheat equation, and the optical properties of the AuNPs were calculated using the discrete dipole approximation method.
The optimal treatment conditions for photothermal therapy were confirmed through the apoptosis ratio, which quantitatively confirms the volume ratio corresponding to the temperature band of apoptosis in tumors, the thermal hazard value that confirms the thermal damage of surrounding normal tissues, and the effective apoptosis ratio that considers the above two variables at the same time.
Finally, the AuNP shape, , , , and that afforded the optimal therapeutic effect were obtained; hence, they can be utilized as the optimal treatment conditions for performing photothermal treatment in the future. In addition, future studies will not simply assume a cylindrical tumor, but rather conduct studies on tumors of various shapes.