Spectrally encoded sers nanoparticles for multiplexed optical detection and image-guided surgery

The development of biocompatible nanoparticles for in-vivo molecular imaging and targeted therapy is an area of considerable current interest across a number of science, engineering, and biomedical disciplines. The basic rationale is that nanometer-sized particles have functional and structural properties that are not available from either discrete molecules or bulk materials. When conjugated with biomolecular targeting ligands such as monoclonal antibodies, peptides or small molecules, these nanoparticles can be used to target malignant tumors with high specificity and affinity. In the "mesoscopic" size range of 10-100 nm diameter, nanoparticles also have large surface areas for conjugating to multiple diagnostic (e.g., optical, radioisotopic, or magnetic) and therapeutic (e.g., anticancer) agents. Recent advances have led to the development of biodegradable nanostructures for drug delivery, iron oxide nanocrystals for magnetic resonance imaging (MRI), quantum dots (QDs) for multiplexed molecular diagnosis and in-vivo imaging, and nanoscale carriers for short-interfering RNA (siRNA) delivery. We have developed biocompatible and nontoxic nanoparticles for in-vivo tumor targeting and detection based on self-assembled nanostructures and pegylated colloidal gold. In particular, 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. A major finding is that small-molecule Raman reporters such as organic dyes are not displaced but are stabilized by thiol-modified polyethylene glycols. These pegylated SERS nanoparticles are 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 are able to target tumor biomarkers such as epidermal growth factor receptors (EGFR) on human cancer cells and in xenograft tumor models.