Peptide-nanoparticle hybrid SERS probe for dynamic detection of active cancer biomarker enzymes

Real-time in situ detection of protease enzymes is crucial for early-stage cancer screening and cell signaling pathway study; however it is difficult to be realized using fluorescence or radioactive probes. Here we devise a hybrid optical probe by incorporating nanocrescent particle and peptides with artificial tag molecules. The peptides have high specificity to PSA, one of the most prominent prostate cancer markers, and a serine protease present in patients' seminal fluid and serum. The extrinsic Raman spectral signal from the tag molecules is enhanced by the nanocrescent and the signal is monitored as the indicator for the peptide digestion in nanomolar PSA concentration and femtoliter reaction volume. Sensitive detection of cancer-related serine protease activity of PSA proteins in low concentrations and small volumes of biofluid is critical to early cancer diagnosis, clinical staging, and therapy. The high reaction specificity of the peptide and the monitored extrinsic Raman signal also minimizes the false detection of other serine proteases and intrinsic Raman signal, which results in a high-fidelity and high-signal-to-noise-ratio cancer nanoprobe. Peptide-conjugated nanocrescents should also be applicable for measuring the intercellular and intracellular activity of other cancer-related proteases and protease activity profiling-enabled cancer cell identification.