Silica-Coated, Waxberry-like Surface-Enhanced Raman Resonant Scattering Tag-Pair with Near-Infrared Raman Dye Encoding: Toward In Vivo Duplexing Detection

Abstract

Surface-enhanced Raman resonant scattering (SERRS) tags encoded with near-infrared (NIR) Raman reporters showed great potential for in vivo detection owing to their ultrasensitivity. However, in vivo signal stability of such tags is a remaining problem due to the lack of suitable silica coating method because the weakly adsorbed NIR reporters tend to detach from traditional gold nanosubstrates in the ethanol-rich and high pH conditions, which are commonly used for silica coating. Herein, we propose a silica coating method for NIR SERRS tags by using waxberry-like gold nanoparticles (NPs) as substrates. The lipid bilayer of the NPs played a crucial role in the coating, which can encapsulate the NIR Raman reporter via hydrophobic interactions and prevent the interference from a harsh medium. Thus, the silicacoated tags well preserved ultrasensitivity of bare tags and simultaneously gained satisfactory signal stability in vivo. Moreover, the coating method is compatible for the encapsulation of a variety of thiol group-free NIR reporters (as exemplified by DTTC, Cy7, IR792, and DIR), relying on which a tag-pair with distinguishable peaks can be screened (labeling with DTTC and Cy7, respectively). In vivo duplexing detection revealed that the tagpair-labeled liposome was cleared faster in the liver than polydopamine NPs within one mouse. The developed method paves an easy way for gaining high-quality SERRS tags and will promote their in vivo multiplex analysis and diagnostics applications.

Surface‐Enhanced Raman Probes Based on Gold Nanomaterials for in vivo Diagnosis and Imaging

“…The interactions between gold nanostructures and other can significantly change the surface properties of the gold nanostructures along with their interactions with biological systems to improve their bioavailability. [71] The gold nanomaterials used to construct SERS probes mainly include AuNPs, [30,[72][73][74][75] AuNSs, [76][77][78][79] AuNRs [13,[80][81][82] and others. [83] The shapes and morphologies of the gold nanostructure are an important parameter affecting the SERS activity.…”

“…As is well known, SERS spectroscopy has the potential not only to analyze small molecules, DNA and proteins in vitro , but also for in vivo diagnosis and bioimaging [21–29] . In addition, SERS spectroscopy possesses the multiplexing detection capability due to its narrow‐band Raman spectral signature and wide excitation wavelength [17,30] . In other words, SERS sensing is a non‐invasive technique with high value for molecular and living cell imaging as well as in vivo diagnosis and imaging [26,31–34] .…”

“…[21][22][23][24][25][26][27][28][29] In addition, SERS spectroscopy possesses the multiplexing detection capability due to its narrow-band Raman spectral signature and wide excitation wavelength. [17,30] In other words, SERS sensing is a non-invasive technique with high value for molecular and living cell imaging as well as in vivo diagnosis and imaging. [26,[31][32][33][34] Compared with traditional medical imaging techniques, SERS imaging can provide high-resolution and molecular information with lower cost.…”

SERS Tags for Biomedical Detection and Bioimaging

“…Encapsulating these dyes into a shell or cavity is an effective strategy to prepare stable and sensitive SERS tags with NIR Raman reporters. By using lipid bilayer to encapsulate the NIR Raman reporters on the surface of Au nanoparticles through hydrophobic interactions, thiol group-free NIR Raman reporters could be modified on the surface of Au nanoparticles 56 . Besides, IR780 perchlorate or IR792 perchlorate can be wrapped by the silica coating layer to produce the SERS tags 57 .…”

“…Monolayered MPTMS or APTMS molecules can attach to the surface of noble nanostructures by forming metal-S or metal-N bonds. Sodium silicate or TEOS are employed to adjust the thickness of silica coating layers ( Figure 3 A) 56 , 61 . Sodium silicate is the optimized silica source for engineering the SERS tags with ultrathin silica layers, and the thick silica coating layers are always formed through the hydrolysis of TEOS.…”