Photothermal Effect of Gold Nanoparticles as a Nanomedicine for Diagnosis and Therapeutics

Abstract

Gold nanoparticles (AuNPs) have received great attention for various medical applications due to their unique physicochemical properties. AuNPs with tunable optical properties in the visible and near-infrared regions have been utilized in a variety of applications such as in vitro diagnostics, in vivo imaging, and therapeutics. Among the applications, this review will pay more attention to recent developments in diagnostic and therapeutic applications based on the photothermal (PT) effect of AuNPs. In particular, the PT effect of AuNPs has played an important role in medical applications utilizing light, such as photoacoustic imaging, photon polymerase chain reaction (PCR), and hyperthermia therapy. First, we discuss the fundamentals of the optical properties in detail to understand the background of the PT effect of AuNPs. For diagnostic applications, the ability of AuNPs to efficiently convert absorbed light energy into heat to generate enhanced acoustic waves can lead to significant enhancements in photoacoustic signal intensity. Integration of the PT effect of AuNPs with PCR may open new opportunities for technological innovation called photonic PCR, where light is used to enable fast and accurate temperature cycling for DNA amplification. Additionally, beyond the existing thermotherapy of AuNPs, the PT effect of AuNPs can be further applied to cancer immunotherapy. Controlled PT damage to cancer cells triggers an immune response, which is useful for obtaining better outcomes in combination with immune checkpoint inhibitors or vaccines. Therefore, this review examines applications to nanomedicine based on the PT effect among the unique optical properties of AuNPs, understands the basic principles, the advantages and disadvantages of each technology, and understands the importance of a multidisciplinary approach. Based on this, it is expected that it will help understand the current status and development direction of new nanoparticle-based disease diagnosis methods and treatment methods, and we hope that it will inspire the development of new innovative technologies.

Keywords: cancer immunotherapy; gold nanoparticles; nanomedicine; photonic PCR; photothermal effect.

Figure 6

Application of various AuNPs in PA imaging. (a) Schematic of 5 nm ultrasmall AuNPs for PA imaging application and (i) cross-sectional images of A431 cells labeled with 5 nm maps for 10 h at different concentrations. (b) Schematic and photographs of photoacoustic imaging of tumor-bearing mice from four different mice samples (m1–m4) using large and miniature AuNRs. (ii,iii) PA imaging for the nontargeted larger and small AuNRs, respectively; (iv,v) PA imaging of the GRPR-targeted large and small AuNRs, respectively. The colored maps, which represent the PA imaging signal intensity, are overlayed with the ultrasound images to provide anatomical information. (c) Schematic of the prepared SiO₂@PEG-AuNR with DOX. (vi) In vivo PA imaging of 4T1 tumor-bearing mice before and after 24 h post-injection. (vii) PET imaging of 4T1 tumor-bearing mice at different time points. Reproduced with permission from [80,83,86]. Copyright 2019, Optical Society of America, Springer Nature 2019, and Elsevier 2018.

Figure 1

Developed diagnostic and therapeutic applications of AuNPs for (a) in vitro diagnosis, (b) in vivo imaging, (c) therapeutic carrier, and (d) phototherapy. Reproduced with permission from [14,15,16,17,18]. Copyright 2021 American Chemical Society; Copyright 2020 Wiley-VCH; Copyright 2009 National Academy of Sciences, USA; Copyright 2015 Wiley-VCH; Copyright 2017 MDPI publisher.

Figure 2

The mechanism of light-driven photothermal effect. Reproduced with permission from [42], Copyright 2019, American Chemical Society.

Figure 3

(a) Near-infrared window of body tissue, (b) calculated extinction spectra of spherical AuNPs, (c) AuNRs, (d) extinction spectra of AuNRs with increased aspect ratio, (e) AuNS, and (f) AuNC. Reproduced with permission from [44,45]. Copyright 2006, Royal Society of Chemistry; Copyright 2018 American Chemical Society.

Figure 4

Design strategy for enhanced PT and PA imaging in AuNPs. (a) Design of r-GO-coated AuNS, (b) Thermal images of GO- and r-GO-coated AuNS using laser source treatment (3.0 W/cm², 808 nm). (c,d) Temperature rise in AuNSs and AuNRs after GO and r-GO coating. (e) Synthesis of r-GO-AuNR via hydrazine (method 1) and light-mediated reduction (method 2). (f) PA images and (g) signal amplitude for AuNR, GO-AuNR, and r-GO-AuNR (laser power = 6.2 mJ/cm²; pulse rate = 10 Hz). (h) AuNR synthesis with controlled silica shell thickness. (i) Temperature variation and (j) photothermal efficiency for AuNR with varying SiO₂ thickness. (k,l) Gold-plated carbon nanotube (GNT), photothermal image, and PA signal using 850 nm laser. (m,n) Comparison of PA signal intensity. * p < 0.05, compared to GNTs for 10 measurements. Reproduced with permission from [61,62,63,65] Copyright @ 2013, 2015, American Chemical Society; Copyright @ 2022, RSC Publishing; Copyright 2009, Nature Publishing Group.

Figure 5

Schematic illustrating the working principle of PAT, and the high-resolution in vivo imaging of melanoma. Reproduced with permission from [70,73], Copyright 2006 and 2016. Nature Publishing Group.

Figure 7

(a) Schematic representation of the AuNBP-based PCR amplification strategy. (b) Associated blue LED system for the amplification of the PCR-based system. (c) Temperature profile obtained for amplification of 30 cycles with different concentrations or OD of AuNBPs and (d) heating and cooling rates calculated for the AuNBPs using a blue LED. (e) Concentration-dependent amplification study of the M13mp18 DNA template. (f) Linear plot of the cycle number crossing points for the DNA amplification with the concentration of M13mp18 DNA. Reproduced with permission from [90]. Copyright 2017, American Chemical Society.

Figure 8

(a) A schematic representation of the Au nanoprism-based nanocarrier for siRNA-PDL-1 complex and their application in cancer immunotherapy. (b) mRNA and (c) protein expressions of hPD-L1 in HCC827 cells after the laser irradiation using PBS as a control (^★ p < 0.05). (d) Confocal microscopic images for HCC827 cells treated with AuNPs and AuNPs-siRNA using 630 nm laser. Reproduced with permission from [156]. Copyright, 2019, Elsevier.

Figure 9

Schematic representation of the Prussian Blue-based nanoparticles showing the optimum thermal dosage for cancer immune therapy. Reproduced with permission from [167]. Copyright 2018, Wiley-VCH.

Figure 10

(a) Cartoon representation of the liposome-based self-assembly of AuNPs, (b) changes in the absorption peaks of AuNPs with varying composition of AuNPs and liposomes, (c) confocal microscopic images for 4T1 tumor cells using calreticulin after PTT treatment, and (d) immunofluorescence staining studies for HMGB1 expression of cancer cells after PTT. Reproduced with permission from [168]. Copyright 2019, American Chemical Society.

Figure 11

(a) Cartoon representation of the combined approach for immunotherapy. (b,c) Tumor growth in primary and distant tumors, respectively, using the combined approach (AuNSTs + Laser + Anti-PD-L1) in various mice (1–5). (d) Percentage of total leukocytes (CD45), total T-cells (CD3), CD4, CD8, and T regulatory cells (CD4/CD25/FOXP3) after the treatment. * p  <  0.05, compared to control group. Reproduced with permission from [173]. Copyright 2017, Springer Nature.