Recent developments in the use of gold and silver nanoparticles in biomedicine

Abstract

Gold and silver nanoparticles (NPs) are widely used in the biomedical research both in the therapeutic and the sensing/diagnostics fronts. Both metals share some common optical properties with surface plasmon resonance being the most widely exploited property in therapeutics and diagnostics. Au NPs exhibit excellent light-to-heat conversion efficiencies and hence have found applications primarily in precision oncology, while Ag NPs have excellent antibacterial properties which can be harnessed in biomaterials' design. Both metals constitute excellent biosensing platforms owing to their plasmonic properties and are now routinely used in various optical platforms. The utilization of Au and Ag NPs in the COVID-19 pandemic was rapidly expanded mostly in biosensing and point-of-care platforms and to some extent in therapeutics. In this review article, the main physicochemical properties of Au and Ag NPs are discussed with selective examples from the recent literature. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Diagnostic Tools > In Vitro Nanoparticle-Based Sensing Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.

Keywords: COVID-19; diagnostics; gold nanoparticles; nanomedicine; silver nanoparticles.

FIGURE 1

(a) Key common and distinct properties of Au and Ag nanoparticles (NPs) in the biomedical field along with representative metrics of the size of the current research and patent landscape; (b,c) depict spherical and anisotropic geometries of Au (spheres, rods, stars, shells, and cages) and Ag (spheres, pyramids, triangles, and cubes) NPs, respectively, that have been explored for biomedical applications, and (d) interaction of a light wave with a spherical metallic NP causing oscillation of the electron cloud on the surface of the NP, giving characteristic absorbance spectra for Au and Ag, which were first described by Mie equations. Copyrights by (b,c) Springer Nature (Cobley et al., ; Raliya et al., 2017), American Chemical Society (Adams et al., ; Skrabalak et al., ; Y. Sun et al., ; Wiley et al., , ; Y.‐Y. Yu et al., ; S. Zhou et al., 2016), and Institute of Physics (Navarro et al., 2012)

FIGURE 2

Schematic and transmission electron microscopy (TEM) images of (a) a spherical nucleic acid (SNA) with Au NP core and a densely packed siRNA and poly(ethylene glycol) shell, (b) poly(ethylene oxide)‐b‐poly(acrylic acid‐r‐styrene)‐b‐poly(styrene)‐SH triblock copolymer self‐assembly of thiol‐capped polymer chains on the surface of Au NPs with patchy anisotropic geometries, and (c) facile anisotropic geometries on the surface of Au NPs by self‐assembly and polymerization of small ionizable ligands (namely, benzene‐1,4‐dithiol [BDT] mixed with other thiol ligands depicted in the inlets) controlled by their respective stoichiometries. Copyrights by (a) Elsevier (Melamed et al., 2018) and (b) American Chemical Society (Y. Yang, Lina, et al., ; J. Zhou et al., 2021)

FIGURE 3

(a) Schematic of DNA‐glued nanorod (NR) dimers further self‐assembled with upconverting nanoparticles (NPs) with Ce6 photosensitizer for multimodal image‐guided combinational phototherapy, (b) representative TEM image of the nanoassemblies, (c) CT imaging of HeLa‐tumor bearing mice 24 h post i.v. injection of the nanoassemblies along with upconversion luminescence in (d) T1‐MR in (e) and photoacoustic imaging in (f). TEM image of a 30‐nm‐sized Au nanostar in (g), near‐infrared imaging of mouse surface temperature during photothermal treatment of primary sarcomas after intravenous injection with Au nanostars with characteristic temperature gradient increase (yellow–orange–red hues) in (h), X‐ray images of mice before and 3 days after photothermal treatment showing significant tumor reduction in (i), CT images of hind leg in primary sarcomas 24‐h postinjection with NPs showing increased NP accumulation at the tumor site (green signal) in (j), coronal CT‐slice of the tumor site 72‐h postinjection showing peripheral NP accumulation at the tumor site in (k), and two‐photon luminescence of Au nanostars with characteristic white signal in (l). TEM images of Au nanocages in (m), photoacoustic (PAT) images showing gradual biodistribution of Au nanocages in normal (top) and orthotopic mouse models (BEL‐7402, bottom) at time intervals up to 24 h in (n), tumor gradual tumor accumulation (green signal) of Au nanocages at the tumor site up to 24 h in (o). Copyrights by (a–f) Wiley (Langer et al., 2020); (g–l) Ivyspring (Y. Liu et al., 2015); and (m–o) Royal Society of Chemistry (Bao et al., 2017)

FIGURE 4

Schematic of the construction of Ag nanoparticle (NP)‐based multifunctional nanoformulation with redox reaction between Ag⁺ and AIEgen in a single‐nanoparticulate form in (a) allowing for multimodal image‐guided tumor treatment in (b). Inflammation targeting and synergistic effects of Ag NPs with porphyrinic porous coordination network for photodynamic therapy (PDT) generated ¹O₂ and Ag⁺ release and targeted metal‐ion therapy (MIT) in (c). Copyright by Elsevier (X. He, Peng, et al., ; L. Zhang et al., 2020)

FIGURE 5

Catechol induced in situ reduction of Ag(I) to form Ag NPs in (a) and Ag NPs as produced by this method in (b). Ag NP embossed PLGA NPs by tannic acid reduction and Fe⁺ coordination in (c) and (d), and their respective TEM images in (e). Selective higher uptake of the NPs by J77a.1 macrophages compared to NIH3T3 fibroblast cells (NPs with red signal in (f)). Copyright by Elsevier (Elnaggar et al., ; Fullenkamp et al., 2012)

FIGURE 6

Time‐resolved evolution of the absorption spectrum of hollow Au–Ag nanoshells with characteristic red‐shifting of the surface plasmon resonance (SPR) band in (a), high‐angle annular dark‐field scanning TEM image of hollow Au–Ag 60‐nm nanoshells with thin shells and large voids in (b). TEM image of Ag‐coated Au nanorods NRs and stripping off of the Ag coating upon exposure of a mild etchant in (c), photoacoustic contrast signal recovery (red signal) upon Ag etching tracked by ultrasound imaging of subcutaneously injected Au–Ag nanorods on a mouse model in (d) and (e). Copyright by American Chemical Society (Kim et al., ; Russo et al., 2018)

FIGURE 7

CRISPR induced MEF with Au NPs; 20 nm Au NPs are coupled with 60 Au NPz via a FITC‐containing double‐stranded DNA (reporter molecule) and a single‐stranded DNA molecule (quenched OFF state). Dequenching (ON state) is achieved by CRISPR‐Cas12a activation via crRNA and target cfDNA by trans‐cleavage effects in (a), naked eye visible color changes of the assay at various stages with characteristic changes upon NP pair formation (purple hue) and dequenching (restoration and MEF signal) events by CRISPR in (b). Schematic showing the characteristic MEF quenching and dequenching of the sensor based on the proximal distance changes between the reporter molecule (5(6)‐carboxyfluorescein as molecular beacon) and the metallic center (Au–Ni–Au rods) in respect to folding/unfolding events of DNA strands in (c), and typical scanning electron microscopy (SEM) image of the magneto‐plasmonic sensors in (d). Copyright by American Chemical Society (J.‐H. Choi et al., ; Lee et al., 2019). CRISPR, clustered regularly interspaced short palindromic repeats; MEF, metal‐enhanced fluorescence; NPs, nanoparticles

FIGURE 8

Fabrication procedure of Si‐patterned surfaces for surface‐enhanced Raman scattering (SERS) in (A) (a,b), SEM images of top and side views of the surfaces (c–f); characteristic bending of the patterned nanostructures on a polyethylene substrate in (B) and typical SERS spectra of flexible and Si patterned surfaces in (C). Copyright by Wiley (B. Liu et al., 2018)