Metal Carbonyl–Gold Nanoparticle Conjugates for Live‐Cell SERS Imaging

Abstract

The field of bioorganometallic chemistry, the junction of organometallic chemistry and biology, is coming of age. In particular, applications of metal carbonyl compounds in biological immunoassays (metallo-immunoassays), pharmaceuticals, CO therapy (CO-releasing molecules), and bioimaging have emerged. [1][2][3][4] One of the useful characteristics of metal carbonyl compounds is the strong CO stretching vibrations in the mid-IR region (1800-2200 cm À1 ); a region that is relatively free of interference from absorbance of biomolecules. This has been utilized in the development of carbonyl immunoassays, [1f] and more recently, in cell imaging, with detection techniques that include FTIR, Raman, and PTIR spectroscopy. [4] Although the first two detection methods can be carried out with readily available instrumentation, a major hindrance to IR detection for live-cell imaging is the interference from a strong absorption band of water at approximately 1600 cm À1 . Although Raman spectroscopy provides a far better spatial resolution with minimal interference from water, [5] it suffers from a low scattering cross section. [6] This necessitates a high concentration of the metal carbonyl based biotag, which poses the problem of undesired cytotoxicity and hence limits its potential in clinical applications. Furthermore, most metal carbonyl compounds have low solubility in water, thus requiring complicated bioconjugation to render them more water soluble or dispersible, and biocompatible. Therefore, there is a need to develop a highly sensitive, targeted, and low-toxicity metal carbonyl based biotag toward eventual biological applications.One promising approach to signal enhancement is surface-enhanced Raman spectroscopy (SERS); the Raman signals of molecules on colloidal gold or silver nanoparticles can be enhanced by several orders of magnitude (typically 10 6 to 10 14 ) as a result of the strong surface plasmon resonance of the nanostructured surface. This spectroscopic method has been successfully adapted to chemical sensing applications, at lower concentrations but with better detection limits, [7] and is exemplified by its use in DNA detection, [8] cancer diagnosis, [9] and detection of cellular molecules. [10] The possibility that SERS may also be used to enhance the CO stretching vibration signal of metal carbonyl compounds is attractive. Furthermore, detection by Raman microscopy will afford spatial resolution into the submicron range.The use of organometallic osmium carbonyl clusters (OM) has been demonstrated earlier; [4a] they have the advantages of being oxygen-and moisture-stable, and are very robust in comparison with other organometallic compounds. The preparation and mode of interaction of osmium carbonyl clusters with the surface of gold nanoparticles (NPs) have also been reported recently. [11] We thus envisage that the binding of an organometallic osmium carbonyl cluster, Os 3 (CO) 10 (m-H) 2 , onto the surface of gold nanoparticles (henceforth designated as "OM-NP") may significantly enhance the i...

Antibody–drug gold nanoantennas with Raman spectroscopic fingerprints for in vivo tumour theranostics

“…[9] Gold nanoparticles (AuNPs) covered by Raman reporters have been used for SERS to detect cancer cells in vitro and tumours in vivo. [10][11][12][13] Raman reporters combined with AuNPs produce an optical contrast to distinguish between cancer and normal cells and their conjugation with antibodies allowed them to determine the expression of relevant biomarkers in molecular imaging. [13] Qian et al reported that, when conjugated to tumour targeting ligands, these SERS-NPs were able to target tumour markers…”

Biocompatible Surface-Enhanced Raman Scattering Nanotags for In Vivo Cancer Detection

“…Anti-HER2 2-(4-(bis(4-(diethylamino)phenyl) (hydroxy)methyl)phenoxy)ethyl 5-(1,2-dithiolan-3-yl)pentane [39] 60-nm gold nanosphere BSA Anti-HER2 CyNAMLA-381 [29] SKBR3; breast and OSCC; head-andneck squamous cell carcinoma 60-nm gold nanosphere PEG Anti-HER2 and anti-EGFR B2LA, Cy3LA [40] OSCC; oral squamous 60-nm gold nanosphere PEG Anti-EGFR Organometallic osmium carbonyl cluster [41] MDA-MB-231; breast 40-nm gold nanosphere Silica Anti-CD24 and -CD44 MGITC [42] Tu686; head-andneck squamous cell carcinoma CHO; ovarian 35-50-nm silver nanoparticles NA Anti-EGF 2,4-dinitrobenzoic acid [43] Gold nanoparticlebased microfluidic chip NA NA 4-mercaptobenzoic acid [44] HEK293; human embryonic kidney 13-nm gold nanosphere…”

Applications of gold nanoparticles in medicine and therapy

“…The synthesized probe produced T2 weighted contrast and was simultaneously used as a SERS active material both in silico and in vivo. Kong et al 164 prepared metal carbonyl based biotags by combining osmium carbonyl clusters and AuNPs, as an example of an organometallic-AuNPs (OMAuNPs) conjugate used to cell SERS imaging. 164 It showed clearly the advantage of transition-metal carbonyl compounds, for which the CO stretching vibration signal was well separated from other molecular vibrational modes of the cells in live-cell imaging.…”