Detection of Inflammation in Vivo by Surface-Enhanced Raman Scattering Provides Higher Sensitivity Than Conventional Fluorescence Imaging

Abstract

The detection of inflammatory changes is a key aim for the early diagnosis and treatment of several autoimmune, infectious, and metastatic diseases. While surface-enhanced Raman scattering (SERS) has the capability to provide noninvasive, in vivo imaging at sufficient depth to achieve this goal, this approach has not been exploited in the study of inflammation. SERS-active nanoparticles were coded with a unique Raman signal that was protected under a wide range of conditions and stimuli. To detect early-stage inflammation, gold nanoparticle clusters containing Raman-active molecules were conjugated to intercellular adhesion molecule 1- (ICAM-1-) specific monoclonal antibodies. SERS allowed noninvasive measurement of ICAM-1 expression in vivo with twice the sensitivity of two-photon fluorescence. This is the first time SERS has been used for in vivo detection of inflammation and is a major advance in the ever-growing toolkit of approaches for use in noninvasive, next-generation in vivo imaging.

Surface enhanced Raman spectroscopy (SERS): Potential applications for disease detection and treatment

“…The nanotags specifically targeted inflammation in vitro, ex vivo and in vivo. [102] When the effectiveness of the SERS approach was directly compared with the conventional fluorescence method it was found to be significantly more sensitive. [102] Whilst the previous examples have demonstrated active in vivo disease targeting, a multi marker approach is considered to be beneficial, especially if multiple disease aspects are to be detected simultaneously.…”

“…[102] When the effectiveness of the SERS approach was directly compared with the conventional fluorescence method it was found to be significantly more sensitive. [102] Whilst the previous examples have demonstrated active in vivo disease targeting, a multi marker approach is considered to be beneficial, especially if multiple disease aspects are to be detected simultaneously. [13] It is hoped that by analysing disease processes or even multiple different diseases it will lead to better characterisation and personalised medicine.…”

Development of nanostars as a biocompatible tumor contrast agent: toward in vivo SERS imaging

“…2,3 Examples for the successful use of the Raman labeling approach are the discrimination of different cell types, viruses, and other lab-on-a-chip applications. [4][5][6][7][8][9] Also in vivo, these SERS-active structures, such as nanorods or nanospheres, have shown the potential to discriminate these labels inside different tissues. 10,11 Gold nanoparticles have been extensively studied as potential SERS contrast agents for cancer diagnosis.…”

Surface-enhanced Raman spectroscopy for in vivo biosensing

“…Indeed, sensitivity is one of the most important factors when designing new diagnostic tests, as early detection of disease improves patients' prognoses. In terms of sensitivity, SERS measurements can be superior to fluorescence-based measurements in vivo, 109 and the former offer greater multiplexing capabilities and specificity due to the unique fingerprint spectra arising from specific molecular vibrations. Certain reporter molecules, such as DTTC, can be utilised for dual-mode imaging using both SERS and fluorescence.…”

“…Although passive targeting is suitable in certain in vivo applications, more commonly employed is active targeting, in which the nanoprobe is functionalized with a recognition moiety. This moiety, which may take the form of an antibody, 109 aptamer 110 or folic acid, 111 allows more sensitive detection of specific antigens in vivo. A lot of in vivo SERS-based biosensing research has focused on cancer detection, in which nanotags are functionalised with antibodies specific to antigens -such as epidermal growth factor receptor (EGFR) and human epidermal growth factor 2 (HER2) -that are overexpressed in tumours.…”