SERS Nanosensors and Nanoreporters: Golden Opportunities in Biomedical Applications

Abstract

This article provides an overview of recent developments and applications of surface-enhanced Raman scattering (SERS) nanosensors and nanoreporters in our laboratory for use in biochemical monitoring, medical diagnostics, and therapy. The design and fabrication of different types of plasmonics-active nanostructures are discussed. The SERS nanosensors can be used in various applications including pH sensing, protein detection, and gene diagnostics. For DNA detection the 'Molecular Sentinel' nanoprobe can be used as a homogenous bioassay in solution or on a chip platform. Gold nanostars provide an excellent multi-modality theranostic platform, combining Raman and SERS with two-photon luminescence (TPL) imaging as well as photodynamic therapy (PDT), and photothermal therapy (PTT). Plasmonics-enhanced and optically modulated delivery of nanostars into brain tumor in live animals was demonstrated; photothermal treatment of tumor vasculature may induce inflammasome activation, thus increasing the permeability of the blood brain-tumor barrier. The imaging method using TPL of gold nanostars provides an unprecedented spatial selectivity for enhanced targeted nanostar delivery to cortical tumor tissue. A quintuple-modality nanoreporter based on gold nanostars for SERS, TPL, magnetic resonance imaging (MRI), computed tomography (CT), and PTT has recently been developed. The possibility of combining spectral selectivity and high sensitivity of the SERS process with the inherent molecular specificity of bioreceptor-based nanoprobes provides a unique multiplex and selective diagnostic modality. Several examples of optical detection using SERS in combination with other detection and treatment modalities are discussed to illustrate the usefulness and potential of SERS nanosensors and nanoreporters for medical applications.

Surface enhanced Raman spectroscopy (SERS) for in vitro diagnostic testing at the point of care

“…SERS is one technique that can enhance the Raman signal by several orders of magnitude by amplifying the electron cloud density around metallic nanostructures [99][100][101]. SERS signal enhancement is achieved through two distinct mechanisms: electromagnetic enhancement and chemical enhancement [100,[102][103][104]. For both mechanisms to occur simultaneously, an analyte must be adsorbed onto or reside very close to a dielectric (often metallic) surface [90].…”

“…For chemical enhancement to occur, a molecule must be able to be bound directly to the surface of the metal so that there is a charge-transfer structure generated, i.e. an electron-hole pair that can mediate the transfer of energy from the metal directly to the molecular bonds of the analyte [103,104].…”

“…Typical SERS signal enhancement factors (EF) are observed between 10 6 and 10 8 [104] with some reporting EFs as high as 10 14 , thereby indicating that single molecule detection is possible [99,107]. The dramatic enhancement seen for SERS signals makes it useful for detecting extremely low analyte concentrations.…”

Advanced Raman Spectroscopy in Nanomedicine

“…Plasmonics-stimulated and optically modulated delivery of nanoparticles into brain tumor in live animals was demonstrated and gold nanoparticle based photothermal treatment of tumor vasculature may stimulate inflammasomes activity, thus increasing the permeability of the blood brain barrier. The imaging method using TPL of gold nanoparticles provides an unprecedented spatial selectivity for targeted nanoparticles delivery to tumor tissue [20].…”

What Potential Does plasmonics-amplified Synergistic Immuno Photothermal Nanotherapy have for Treatment of cancer?

“…A special type of metallic nanoparticles, called 'plasmonic' nanoparticles, has received great interest because they exhibit enhanced optical and electromagnetic properties. Our fundamental studies of various plasmonic structures [8][9][10] and applied development of plasmonic nanoplatforms have led to a wide variety of applications ranging from chemical sensing [10][11][12] to cancer diagnostics [13][14][15][16][17] and therapy using nanoparticle-mediated photothermal treatment [15,[18][19][20]. Recently, we demonstrated that the use of plasmonic gold nanostars (GNS) in combination with immunotherapy -a treatment we referred to as Synergistic Immuno Photothermal Nanotherapy (SYMPHONY) -can dramatically enhance the efficacy of immunotherapy.…”