Plasmonic Photothermal Nanoparticles for Biomedical Applications

Abstract

Recent advances of plasmonic nanoparticles include fascinating developments in the fields of energy, catalyst chemistry, optics, biotechnology, and medicine. The plasmonic photothermal properties of metallic nanoparticles are of enormous interest in biomedical fields because of their strong and tunable optical response and the capability to manipulate the photothermal effect by an external light source. To date, most biomedical applications using photothermal nanoparticles have focused on photothermal therapy; however, to fully realize the potential of these particles for clinical and other applications, the fundamental properties of photothermal nanoparticles need to be better understood and controlled, and the photothermal effect-based diagnosis, treatment, and theranostics should be thoroughly explored. This Progress Report summarizes recent advances in the understanding and applications of plasmonic photothermal nanoparticles, particularly for sensing, imaging, therapy, and drug delivery, and discusses the future directions of these fields.

Keywords: metal nanoparticles; phothermal effect; photothermal therapy; plasmonic nanoparticles; theranostics.

Figure 1

Representative features of photothermal nanoparticles and their biomedical applications.

Figure 2

Size and shape‐dependent absorption, scattering, and extinction properties of plasmonic nanoparticles. a) Calculated spectra of optical efficiency for gold nanospheres with different diameters (D): 20 nm (left), 40 nm (middle), and 80 nm (right). The red‐dashed, black‐dotted, and green solid lines indicate the efficiencies of absorption, scattering, and extinction for gold nanospheres, respectively. As the size of nanosphere increases, the contribution of absorption and scattering to the total extinction decreases and increases, respectively. b–d) Size‐dependent changes in the relative ratio of scattering to absorption cross‐sections (C _sca/C _abs) of nanoparticles: b) gold nanosphere, c) gold nanorod, and d) silica–gold nanoshell. In case of the nanoshell, the total particle radius (R ₂) are varied (70, 105, and 140 nm) for a fixed ratio of the core radius (R ₁) to the total particle radius (R ₁/R ₂ = 0.857). In case of the nanorod, the effective nanorod radius (r _eff) that determines the volume (V) of the nanorod [r _eff = (3V/4π)^1/3] varied (8.74, 11.43, 17.9, and 21.86 nm) at a fixed aspect ratio of 3.9. Reproduced with permission.26 Copyright 2006, American Chemical Society. e) 3D mapping of the heat power density of different shaped colloidal gold nanoparticles (nanosphere and nanorod) at their respective LSPR conditions. Cross‐sectional images (right side) reveal the heating power density of the inner parts of each nanostructure. Reproduced with permission.28 Copyright 2009, AIP Publishing.

Figure 3

Photoexcitation and relaxation process of LSP on metallic nanoparticles. a) Photoexcitation of localized surface plasmon. b–d) Schematic illustrations of the population of the electronic states during relaxation of the photoexcited localized surface plasmon. The electronic states, hot electrons, and hot holes are depicted by grey, red, and blue, respectively. E _F: Fermi energy. b) Landau damping. On a timescale of 1–100 fs, hot electron–hole pairs are created, and their energy is nonthermally distributed. c) Carrier relaxation. On a timescale of 100 fs to 1 ps, the energy of hot carriers (i.e., hot electrons and hot holes) are redistributed by the electron–electron scattering process. d) Thermal dissipation. On a timescale of 100 ps to 10 ns, the photoexcited energy transferred to the metallic lattice through electron–phonon collisions is released to the surroundings of the metallic nanoparticles in the form of heat. Reproduced with permission.30 Copyright 2015, Springer Nature.

Figure 4

Size‐ and shape‐dependent tunability of optical properties of plasmonic nanoparticles. a) Ultraviolet–visible (UV–vis) absorption spectra of spherical‐shaped gold nanoparticles in water. All spectra were normalized at their LSPR absorption maxima (λ_max; unit of nanometer). As the particle diameter increases, the plasmon absorption red‐shifts: λ_max = 517, 521, 533, and 575 nm for the 9, 22, 48, and 99 nm particles, respectively. Reproduced with permission.50 Copyright 1999, American Chemical Society. b) Surface plasmon absorption spectra of gold nanorods with different aspect ratios (i.e., length‐to‐width ratio). As the aspect ratio of gold nanorod increases (aspect ratios of 2.4, 2.7, 3.6, 4.4, and 6.1 for black, red, blue, magenta, and green spectra, respectively), the longitudinal plasmonic absorption band red‐shifts from the visible to the NIR region, while the transverse plasmonic absorption band rarely changes, regardless of the aspect ratio. Reproduced with permission.[qv: 51a] Copyright 2016, Royal Society of Chemistry. c) Tuning the LSPR wavelength of the 80 nm diameter core–gold nanoshells in water with different shell thickness (t): t = 40, 30, 20, 10, 8, and 4 nm. All the extinction efficiency (Q _ext) spectra were calculated by using an extended Mie theory simulation. As the shell thickness decreases from 40 to 4 nm, the LSPR wavelength red‐shifts progressively from the visible to the NIR region and the extinction efficiency increases. Reproduced with permission.[qv: 51b] Copyright 2007, American Chemical Society. d) UV–vis extinction spectra of gold nanocages with the walls of different thicknesses and porosities. As the volume of HAuCl₄ solution labeled on each curve increases (i.e., increasing the degree of galvanic replacement reaction), the LSPR peaks continuously red‐shifts from the visible to the NIR region due to the structural changes from the silver nanocube to the gold nanocage. e) Comparison of the absorption, scattering, and extinction spectra for gold nanorod (top), nanoshell (middle), and nanocage (bottom). All the optical spectra were obtained from the DDA calculation method, and the LSPR peaks were adjusted to exactly 800 nm for all the nanostructures. Reproduced with permission.[qv: 21b] Copyright 2006, Royal Society of Chemistry.

Figure 5

Plasmonic photothermal nanoparticle‐based biodiagnostics. a) Scheme and results of thermal contrast‐based lateral flow tests for immunoassays. While the visual contrast of AuNPs is insufficient, thermal contrast can detect the target at low concentrations with clear signals. Reproduced with permission.82 Copyright 2012, Wiley‐VCH. b) Photothermal detection of single molecules using AuNRs without labelling or amplification in real time. The steps in the photothermal time trace data show real‐time single‐molecule binding and unbinding events. Reproduced with permission.8 Copyright 2012, Springer Nature. c) Photothermal fluorescence quenching‐based immunoassay method. The data plots show normalized fluorescence emission as a function of streptavidin concentration. Each data point corresponds to the average of five replications by multiple on/off cycles of the NIR laser (inset). Reproduced with permission.89 Copyright 2016, American Chemical Society. d) Plasmonic photothermal nucleic acid amplification using AuBPs. The data shows temperature profiles of 30 thermocycles with different concentrations of particles and real‐time amplification curves obtained from different concentrations of target template. Reproduced with permission.92 Copyright 2017, American Chemical Society. e) Scheme of PNB diagnostics of residual microtumors and cancer cells in vivo. The acoustic signal from PNBs (red line) indicates a single cancer cell in solid tissue [normal cells (green line)]. Reproduced with permission.94 Copyright 2016, Springer Nature.

Figure 6

Photothermal microscope and thermal contrast images. a) Typical experimental setup for photothermal imaging. PBS: polarizing beam splitter; λ/4: quarter wave plate. Reproduced with permission.101 Copyright 2014, The Royal Microscopical Society, published by John Wiley and Sons. b) Differential interference contrast image (left) and two photothermal images (middle and right) of sample mixture with 300 nm latex spheres, and 80 and 10 nm gold spheres. In photothermal images, the intensity of the heating laser was 30 kW cm⁻² (middle) and 1.5 MW cm⁻² (right), respectively. Reproduced with permission.86 Copyright 2002, The American Association for the Advancement of Science. c) Transmission electron microscope images of gold nanostar (AuNS) with different surface functionalization: 1) unmodified AuNS, or AuNS modified with 2) PEG, 3) pep, 4) pep@HA, and 5) pep/DOX@HA. PEG: poly(ethylene glycol); HAase: hyaluronidase. (Bottom left) Temperature changes of nanoplatform solution with NIR irradiation (808 nm, 1 W cm⁻²). The concentration of Au was 4 µg mL⁻¹. (Bottom right) Au concentration‐dependent temperature changes of AuNS‐pep/DOX@HA solution with NIR irradiation (808 nm, 1 W cm⁻²). Insets show photothermal images of the AuNS‐pep/DOX@HA solution at the final temperature. d) (Left) In vivo photothermal imaging of mice injected intravenously with different solution: 1) PBS, 2) AuNS‐PEG, 3) AuNS‐pep@HA, and 4) AuNS‐pep/DOX@HA (left). All images were acquired with NIR laser irradiation (808 nm, 1 W cm⁻²) at 12 h postinjection. (Right) In vivo photothermal imaging of mice intravenously injected with AuNS‐pep/DOX@HA irradiated with NIR laser (808 nm, 1 W cm⁻², for 0, 1, 2, 3, 4, 5 min) at different time points (4, 8, 12, 24 h) after injection (right). Reproduced with permission.[qv: 104a] Copyright 2016, Elsevier.

Figure 7

Various shapes of plasmonic nanoparticles for PPT/PDT applications. a) Transmission electron microscope images and UV–vis spectra of aqueous suspensions of plasmonic gold nanostructures with different morphologies: nanohexapods (top), nanorods (middle), nanocages (bottom). b) Plots of temperature rise as a function of laser irradiation time (top left) and plots of average temperature increase within the in vivo tumor region as a function of laser irradiation time (bottom left), and thermographs of tumor‐bearing mice after photothermal treatment for different periods of time (right). c) ¹⁸F‐flourodeoxyglucose PET/CT images of tumor‐bearing mice intravenously administrated with aqueous suspensions of PEGylated gold nanostructures or saline. Tumors on the left side (white circle + arrow) were treated with laser irradiation while those on the right side (white circle) were not treated. Reproduced with permission.125 Copyright 2013, American Chemical Society. d) Transmission electron microscope images of CPNs with different length and density of nanopetals, synthesized by increasing amounts of gold precursor from CPN‐1 to CPN‐4. Plots of temperature rise (top right) and the generation of ¹O₂ (bottom right) as a function of laser irradiation time for different gold nanoparticles, and cell death with or without laser irradiation (bottom left). Green and red fluorescence indicate live and dead cells, respectively. Reproduced with permission.[qv: 123b] Copyright 2014, American Chemical Society. e) Scheme of GNR@SiO₂‐CDs for dual‐modal PTT/PDT therapy. GNR: gold nanorod. Fluorescence images of calcein acetoxymethyl ester and propidium iodide costaining of cancer cells incubated with GNR@SiO₂‐CDs under laser irradiation: 635 nm (PDT), 808 nm (PTT), and combination (PDT + PTT). Green and red fluorescence indicate live and dead cells, respectively. Reproduced with permission.[qv: 109b] Copyright 2016, Royal Society of Chemistry.

Figure 8

Photothermal nanostructures for drug delivery. a) siRNA and ssDNA delivery system using Au nanoshell (NS). Fluorescence images show H1299 cells incubated with NS‐PLL‐ssDNA. Upon laser irradiation, ssDNA tagged with Alexa Fluor 488 is released, resulting in brighter green fluorescence due to elimination of quenching. The histogram shows downregulation of green fluorescent protein (GFP) in H1299 GFP/red fluorescent protein (RFP) cell line by antisense ssDNA and siRNA. Percent GFP/RFP fluorescence at 18 h (6 h after laser treatment). Reproduced with permission.[qv: 140b] Copyright 2012, American Chemical Society. b) Schematic illustrating the controlled‐release system of AuNC. Cell viability test: (C‐1) cells pulsed laser irradiated for 2 min without AuNCs; (C‐2) cells laser irradiated for 2 min with DOX‐free AuNCs; and (2/5 min) cells laser irradiated for 2 and 5 min with DOX‐loaded AuNCs. Reproduced with permission.[qv: 64c] Copyright 2009, Springer Nature. c) Synthetic process and NIR laser‐induced targeted thermo‐chemotherapy of the nanocomposite. Reproduced with permission.143 Copyright 2014, American Chemical Society. d) Photosensitizer (Ce6)‐loaded gold vesicles (GVs) for trimodality fluorescence/thermal/photoacoustic imaging guided synergistic photothermal/photodynamic cancer therapy. Thermal images show tumor‐bearing (red circles) mice laser‐irradiated post injection of GV‐Ce6. Reproduced with permission.147 Copyright 2013, American Chemical Society. e) Cell‐targeted photocontrolled nuclear‐uptake nanodrug delivery system for cancer therapy. Reproduced with permission.149 Copyright 2014, American Chemical Society.