SERS Nanoprobes in Biologically Raman Silent Region for Tumor Cell Imaging and In Vivo Tumor Spectral Detection in Mice

Abstract

Surface enhanced Raman scattering (SERS) is widely used in biological applications due to its high sensitivity and deep tissue penetration. Most SERS nanoprobes with fluorophore attachments have Raman signals between 1400 and 1700 cm−1. Here, a series of SERS nanoprobes anchored with alkyne moieties in the biologically Raman‐silent region through CAu bond formation is prepared. To achieve target‐specific recognition, two nucleic acid aptamers (AS1411 and MUC1) and two control oligonucleotides (C‐con and T‐con) with the same alkyne moiety are also attached on the Au surface, respectively. Both aptamer‐charged SERS nanoprobes successfully target MCF‐7 cells, which could possibly achieve cross‐check of target cells and overcome the possible false positive results. And the limit of detection reaches up to five cancer cells, which has great potential in circulating tumor cells detection. Further in vivo studies indicate that both SERS nanoprobes are successfully employed to target tumors in living mice with an obvious signal (≈2205 cm−1) at the Raman silent region after tail intravenous injection for the first time.

Bioorthogonal SERS Nanotags as a Precision Theranostic Platform for in Vivo SERS Imaging and Cancer Photothermal Therapy

“…Lipoic acid-modified oligonucleotides with dithiolane groups were synthesized as indicated in Figure c and were further characterized by ion trap mass spectrometry (see Supporting Information). Raman reporter and oligonucleotide were covalently anchored on the surface of AuNR through double Au–S bond after opening the disulfide bond of dithiolane using 10 mM of dithiothreitol (DTT), which demonstrated much better stability than the single Au–S bond. , In our previous article, we found that the optimized molar ratio of 5:1 for pure Raman reporter and its labeled aptamer on gold nanoparticles was good enough for targeting cellular uptake and nanoparticle stability . Therefore, we modified the AuNR with the molar ratio of 5:1 for Raman reporter and lipoic acid labeled oligonucleotide.…”

“…51,52 In our previous article, we found that the optimized molar ratio of 5:1 for pure Raman reporter and its labeled aptamer on gold nanoparticles was good enough for targeting cellular uptake and nanoparticle stability. 50 Therefore, we modified the AuNR with the molar ratio of 5:1 for Raman reporter and lipoic acid labeled oligonucleotide. As displayed in the transmission electron microscopy (TEM) image, CTABcoated AuNR had an aspect ratio of ∼3.8 with around 50 nm in length and 13 nm in width (Figure 2A).…”

Aptamers used for molecular imaging and theranostics - recent developments

“…Mice with MCF-7 tumor xenografts were intravenously injected with 0.6 nmol of the SERS nanoprobe and images of the tumor region taken 4 h later with a slit scanning Raman microscope. Both AS1411 and MUC1 targeted nanoprobes were clearly detected in the tumor while no signal was observed for non-targeted nanoprobes 107 . As an evolution of this design, they created a multiplexed cocktail of AS1411-, RGD peptide- and anti-CD44 antibody targeted SERS probes with distinct Raman reporter functionalities (azide (2120 cm -1 ), diynyl (2205 cm -1 ) and cyano (2230 cm -1 ), respectively).…”

Microfluidic-SERS Technologies for CTC: A Perspective on Clinical Translation

“…Furthermore, the adoption of recently developed alkyne Raman reporters helps overcome issues typically associated with traditional Raman reporters, including problems such as oxidation, spectral overlap, and disruption from complex backgrounds. Their Raman signals in the Raman-silent region (1800–2800 cm –1 ) remain entirely unaffected by various backgrounds, enabling precise detection. , …”

“…Their Raman signals in the Raman-silent region (1800−2800 cm −1 ) remain entirely unaffected by various backgrounds, enabling precise detection. 82,83 Combining SERS nanotags with various Raman reporters' functionalization allows for multiplex detection. This is accomplished by incorporating several SERS nanotags into a sample, each featuring unique Raman spectral characteristics.…”