Gold nanomaterials for optical biosensing and bioimaging

Abstract

Gold nanoparticles (AuNPs) are highly compelling nanomaterials for biomedical studies due to their unique optical properties. By leveraging the versatile optical properties of different gold nanostructures, the performance of biosensing and biomedical imaging can be dramatically improved in terms of their sensitivity, specificity, speed, contrast, resolution and penetration depth. Here we review recent advances of optical biosensing and bioimaging techniques based on three major optical properties of AuNPs: surface plasmon resonance, surface enhanced Raman scattering and luminescence. We summarize the fabrication methods and optical properties of different types of AuNPs, highlight the emerging applications of these AuNPs for novel optical biosensors and biomedical imaging innovations, and discuss the future trends of AuNP-based optical biosensors and bioimaging as well as the challenges of implementing these techniques in preclinical and clinical investigations.

Fig. 1. Au nanostructures of different shapes and sizes with potential applications in optical biosensing and bioimaging: (A) 16 nm AuNS; (B) AuNR; (C) Au nanorice; (D) AuNSh; (E) AuNC; (F) tipless AuNPy; (G) AuNRg; (H) AuNSt; (I) AuNPr; (J) AuNBP; (K) AuND; and (L) AuNCr. Figures are adapted from references with permission. Copyright (2003, 2006, 2007, 2011, 2017) American Chemical Society. Copyright (2009) Elsevier Ltd.

Fig. 2. Various optical biosensing and bioimaging techniques based on AuNPs.

Fig. 3. AuNP-based optical biosensors. (A–E) A smartphone-based biosensor for colorimetric detection of E. coli O157:H7. (A) General schematic of the functioning of the biosensor; (B) results of mixing AuNPs with different combinations of cross-linking agents; (C) hue of the mixtures of the AuNPs with different combinations of cross-linking agents; (D) TEM image of the AuNPs before aggregation; (E) TEM image of the AuNPs after aggregation. Figures have been adapted from ref. with permission from Elsevier, copyright 2019. (F and G) A AuNP-based Cys detection biosensor; (F) working principle of the biosensor and (G) SPR band intensity changes for β-CD AuNPs in the presence of incremental addition of Cys (the inset shows the digital images of β-CD AuNPs in the absence (i) and presence (ii) of Cys). Figures have been adapted from ref. with permission from the Royal Society of Chemistry, copyright 2020.

Fig. 4. Dark-field microscopy images of normal and two different types of cancer cells after incubating with AuNS/AuNR conjugated with anti-EGFR antibodies. AuNS show green to yellow color in the dark-field image (upper panel), indicating that their light scattering is mostly in the visible region. AuNR show orange to red color in the dark-field image (lower panel), indicating that their light scattering is mostly in the NIR region. Modified and reprinted with permission from ref. . Copyright (2006) American Chemical Society.

Fig. 5. AuNPr as OCT contrast agents for contrast enhanced vascular imaging and ozone sensing. (A and B) TEM image and extinction spectrum of AuNPr which have strong plasmonic scattering in the NIR-II region. (C and D) The OCT angiograms of a melanoma tumor implanted on a mouse ear before and after systematically injecting the NIR-II AuNPr. Reprinted with permission from ref. . Copyright (2018) American Chemical Society. (E–G) Geometric and plasmonic evolution of AuNPr upon exposure to ozone (O₃). Upon exposure to O₃, the corners of AuNPr are gradually rounded and the LSPR of AuNPr exhibits a blue shift accordingly. (H) OCT images of a AuNPr-infiltrated crucian carp eye before and at 172 min post exposure of 75 ppm O₃. Reprinted with permission from ref. . Copyright (2017) American Chemical Society.

Fig. 6. Small AuNRs enhanced PA imaging. (A) TEM images of small and large AuNRs. (B) PA signal intensities of small and large AuNRs upon illumination with 200 laser pulses at 18.2 mJ cm⁻². (C and D) PA images of tumor-bearing mice after administration of prostate cancer targeting GRPR peptide-functionalized large and small AuNRs. Reprinted with permission from ref. . Copyright (2019) Springer Nature.

Fig. 7. SERS-based LFA for KSHV detection. (A) Scheme of the LFA biosensor for the simultaneous detection of two nucleic acids. The strip consists of two test lines and one control line. (B) (i) KSHV DNA–Au NP complexes were captured by the probe KSHV DNA on the first test line; (ii) BA DNA–Au NP complexes were captured by the probe BA DNA on the second test line, and (iii) excess KSHV and BA detection DNA attached to AuNPs were captured by control DNA through T20–A20 hybridization on the third control line. (C) Digital photographic images and (D) corresponding SERS spectra of the SERS-based LFA biosensor in the presence of (i) KSHV, 0 pM; BA, 0 pM; (ii) KSHV, 100 pM; BA, 0 pM; (iii) KSHV, 0 pM; BA, 100 pM; (iv) KSHV, 100 pM; BA, 100 pM. Assay time: 20 min. Reprinted with permission from ref. . Copyright (2017) American Chemical Society.

Fig. 8. Multiplexed SERS immunoimaging using AuNSt. (A) TEM images of AuNSt used for SERS. (B) Scheme of AuNSt functionalized with two different Raman-active tag/targeting antibody pairs. The Raman tag pMAB is paired with anti-EGFR, and DTNB is paired with anti-PD-L1. (C) Schematic illustration of the SERS setup for multiplexed tumor immunoimaging. (D) The SERS signals of both DTNB (1325 cm⁻¹) and pMBA (1580 cm⁻¹) in ex vivo mouse breast cancer tissue. Subsection (i) shows a region of interest (ROI) with little AuNSt accumulation, whereas subsection (ii) shows a ROI with rich AuNSt accumulation. (E) The corresponding Raman spectra of ROI (1)–(4) in (D), where (1) shows no AuNSt binding, (2) shows high PD-L1 expression, (3) shows high EGRF expression and (4) shows high expressions of both PD-L1 and EGFR. Reprinted with permission from ref. . Copyright (2018) the Royal Society of Chemistry.

Peng Si

Nasrin Razmi

Chandra Mouli Pandey

Bansi D Malhotra

Magnus Willander

Adam de la Zerda