Precise visualization of tumor margins with characterization of microscopic tumor invasion are unmet needs in prostate oncology that demand approaches with high sensitivity and specificity. To address those needs we report surface-enhanced Raman scattering (SERS) based optical imaging for prostate cancer using a combination of live cell Raman microscopy, optimally engineered SERS tags and a urea-based small-molecule inhibitor of prostate-specific membrane antigen (PSMA) as a targeting moiety. We develop gold nanostar based SERS agents that offer ultrahigh binding affinity to PSMA with nearly four orders of magnitude lower IC50 values in relation to existing clinical imaging agents. This combination enables selective recognition of prostate cancer cells, and facilitates quantitative and photostable Raman measurements. Using Raman microscopy to analyze phenotypically similar prostate cancer cell lines differing only in PSMA expression, we demonstrate facile, site-selective recognition using as low as 20 pM of the SERS agent for imaging, opening the door for spectroscopic detection of prostate and other PSMA-expressing tumors in vivo.
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