Abstract
The purpose of this study was to investigate the effect of photothermal treatment (PTT) with gold nanoshell (ANS) using a macrophage-mediated delivery system in a head and neck squamous cell carcinoma (HNSCC) cell line. To achieve this, ANS-loaded rat macrophages (ANS-MAs) were prepared via the coculture method with ANS. The human HNSCC (FaDu cell) and macrophage (rat macrophage; NR8383 cell) hybrid spheroid models were generated by the centrifugation method to determine the possibility of using ANS-MAs as a cancer therapy. These ANS-MAs were set into the tumor and macrophage hybrid spheroid model to measure PTT efficacy. Kinetic analysis of the spheroid growth pattern revealed that this PTT process caused a decreasing pattern in the volume of the hybrid model containing ANS-MAs (p < 0.001). Comparison with empty macrophages showed harmony between ANS and laser irradiation for the generation of PTT. An annexin V/dead cell marker assay indicated that the PTT-treated hybrid model induced increasing apoptosis and dead cells. Further studies on the toxicity of ANS-MAs are needed to reveal whether it can be considered biocompatible. In summary, the ANS was prepared with a macrophage as the delivery method and protective carrier. The ANS was successfully localized to the macrophages, and their photoabsorption property was stationary. This strategy showed significant growth inhibition of the tumor and macrophage spheroid model under NIR laser irradiation. In vivo toxicology results suggest that ANS-MA is a promising candidate for a biocompatible strategy to overcome the limitations of fabricated nanomaterials. This ANS-MA delivery and PTT strategy may potentially lead to improvements in the quality of life of patients with HNSCC by providing a biocompatible, minimally invasive modality for cancer treatment.
Highlights
IntroductionPhoto-based therapy is a newly developed therapeutic strategy with unique advantages including high specificity, minimal invasiveness, and precise spatial-temporal selectivity. Photothermal therapy (PTT), a type of photo-based therapy, has been developed for the eradication of cancer cells in the primary tumor and the initial stage of cancer metastasis. PTT can also be combined with current therapies to improve their therapeutic outcomes [1,2,3,4]. The therapeutic efficacy of PTT depends on the transformation of light to sufficient heat with photothermal agents such as metal nanostructures, nanocarbons, and organic agents [1]. Metallic nanoparticles are preferable photothermal agents due to their potential applications with tunable optical activities. Metallic nanoparticles have unique optical properties due to the interaction between light and the free conductionband electrons on the surface of the particles. The electric field causes the collective oscillation of the conductionband electrons on the surface of the nanoparticles under suitable light conditions. This phenomenon, termed surface plasmon resonance (SPR), makes metallic nanoparticles attractive to cancer treatment researchers [5]. Many researchers have tried to improve the inherent properties of the metallic nanoparticles by employing several strategies such as changing the nanostructure and using multiple metallic compound combinations. The combination of the Fe7S8 and Bi2S3 metallic compounds helps create a large surface area for effective drug loading and provides high NIR absorption for enhanced photothermal efficacy [3]. Thus, the combination of the two metal structures showed 1.54 times higher NIR absorption intensity than that of pure Bi2S3 nanomaterials [3]. Zhang et al have developed the superstructure of CuS for use in chemo-photothermal therapy; this CuS was biodegradable, which enabled its use in synergistic chemo-photothermal therapy [4]
The black dots indicate ANS accumulation in the macrophage. These dark areas are absent in the control macrophages that were not incubated with ANS
These microscopic, holographic, and EDX images indicate that the ANS were successfully inserted into the macrophage and their physical properties were safely maintained after the cell loading process
Summary
Photo-based therapy is a newly developed therapeutic strategy with unique advantages including high specificity, minimal invasiveness, and precise spatial-temporal selectivity. Photothermal therapy (PTT), a type of photo-based therapy, has been developed for the eradication of cancer cells in the primary tumor and the initial stage of cancer metastasis. PTT can also be combined with current therapies to improve their therapeutic outcomes [1,2,3,4]. The therapeutic efficacy of PTT depends on the transformation of light to sufficient heat with photothermal agents such as metal nanostructures, nanocarbons, and organic agents [1]. Metallic nanoparticles are preferable photothermal agents due to their potential applications with tunable optical activities. Metallic nanoparticles have unique optical properties due to the interaction between light and the free conductionband electrons on the surface of the particles. The electric field causes the collective oscillation of the conductionband electrons on the surface of the nanoparticles under suitable light conditions. This phenomenon, termed surface plasmon resonance (SPR), makes metallic nanoparticles attractive to cancer treatment researchers [5]. Many researchers have tried to improve the inherent properties of the metallic nanoparticles by employing several strategies such as changing the nanostructure and using multiple metallic compound combinations. The combination of the Fe7S8 and Bi2S3 metallic compounds helps create a large surface area for effective drug loading and provides high NIR absorption for enhanced photothermal efficacy [3]. Thus, the combination of the two metal structures showed 1.54 times higher NIR absorption intensity than that of pure Bi2S3 nanomaterials [3]. Zhang et al have developed the superstructure of CuS for use in chemo-photothermal therapy; this CuS was biodegradable, which enabled its use in synergistic chemo-photothermal therapy [4].
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