Targeted Live Cell Raman Imaging and Visualization of Cancer Biomarkers with Thermal‐Stimuli Responsive Imprinted Nanoprobes

Abstract

AbstractPrecise visualization of cancer biomarkers within live cells is significantly vital in oncology that requires techniques with high specificity and selectivity. Herein, a new imprinted plasmonic nanoprobe with thermosensitivity is fabricated, which features multifunctional roles as an “artificial antibody” for the active targeting of cancer biomarkers triggered by temperature and can also achieve their in situ Raman detection and imaging within living cells. A thiol‐containing poly(N‐isopropylacrylamide) linear polymer is first synthesized using reversible addition–fragmentation chain transfer polymerization followed by further reduction with NaBH4 to produce free thiol groups at one end. Then, plasmonic nanoprobes are constructed by creating protein‐imprinted poly(N‐isopropylacrylamide) self‐assembled monolayers on the surface of gold nanorods. High specificity and selectivity are demonstrated for the target protein, with an extracellular Raman detection limit of 10−14 mol L−1. Thermally responsive behavior is achieved by modulating the external temperature. The plasmonic properties enable in situ live cell intracellular Raman detection and imaging of endogenous cancer biomarker epidermal growth factor receptor. This technique offers significant promise for visualizing cancer biomarkers and monitoring molecular mechanisms both in vitro and in vivo, which are significant in clinical diagnosis and medical theranostics.