In vivo tumor targeting and spectroscopic detection with surface-enhanced Raman nanoparticle tags

Abstract

We describe biocompatible and nontoxic nanoparticles for in vivo tumor targeting and detection based on pegylated gold nanoparticles and surface-enhanced Raman scattering (SERS). Colloidal gold has been safely used to treat rheumatoid arthritis for 50 years, and has recently been found to amplify the efficiency of Raman scattering by 14-15 orders of magnitude. Here we show that large optical enhancements can be achieved under in vivo conditions for tumor detection in live animals. An important finding is that small-molecule Raman reporters such as organic dyes were not displaced but were stabilized by thiol-modified polyethylene glycols. These pegylated SERS nanoparticles were considerably brighter than semiconductor quantum dots with light emission in the near-infrared window. When conjugated to tumor-targeting ligands such as single-chain variable fragment (ScFv) antibodies, the conjugated nanoparticles were able to target tumor biomarkers such as epidermal growth factor receptors on human cancer cells and in xenograft tumor models.

Plasmonics in atomically thin materials

“…Additionally, and unlike other optical excitations in small systems (e.g., atomic and molecular quantum emitters), plasmons display a powerful combination of two appealing properties: they are robust (i.e., they are not destroyed by the presence of a dielectric environment) and they interact strongly with light (e.g., they display excitation crosssections typically exceeding the projected area of the nanostructures that sustain the plasmons). These features have facilitated the use of plasmons in applications as varied as nonlinear optics [2][3][4][5], ultrasensitive detection down to the single-molecule level via surface-enhanced Raman scattering (SERS) [6][7][8][9], cancer diagnosis and therapy [10][11][12][13][14][15], quantum information processing [16][17][18][19], improved photovoltaics [20,21], and subwavelength lithography [22]. Optical metamaterials are also largely relying on subwavelength plasmons to display properties that are not available in naturally occurring materials [23][24][25].…”

Application of nanoparticles in cancer detection by Raman scattering based techniques

“…AuNPs can easily be functionalized with antibodies and other tumor targeting biomolecules through well-established conjugation procedures [49,50]. In recent years, several groups [51, 52] have demonstrated the potential of using AuNPs based on Raman tags for SERS. Depending on the location of the tumor tissue, a variety of AuNPs were  used for SERS.…”

“…Qian et al, in the first study of whole-animal Raman imaging in a multiplexed manner, exploited PEGylated Au nanoparticle and SERS, but they conjugated SERS nanoparticles with a ScFv antibody, a ligand that binds to EGFR with high specificity and affinity, for in vitro and in vivo tumor targeting. They asserted that their technique could detect deep tumors as accurately as superficial ones, and highlighted the sensitivity, specificity and non-toxicity of the technique and respective nanoparticles [51]. Dinish et al [73] performed actively targeted multiplex in vitro and in vivo detection of three intrinsic cancer biomarkers, EGFR, CD44 and TGF beta-receptor II (TGFbRII), in a breast cancer model using three multiplexing capable and biocompatible SERS.…”

Controllable Cobalt Oxide/Au Hierarchically Nanostructured Electrode for Nonenzymatic Glucose Sensing

“…However, Ag is considered unstable, degrades in vivo and is typically synthesized with cetrimonium bromide (CTAB), which is considered cytotoxic [282][283][284]. Additionally, it has been demonstrated that the peak intensity ratios of the Raman signal change significantly when silver aggregates are used leading to inconsistent results and poor reproducibility [276,[285][286][287].…”