AS1411 aptamer-functionalized, cell membrane-camouflaged nanoparticles for targeted tumor cells imaging in the Raman...

Surface-enhanced Raman scattering (SERS) technology has attracted increasing attention in the field of biological imaging. Herein, we designed a new biomimetic SERS nanoprobe by sequentially modifying 4-mercaptobenzonitrile (4-MBN), cell membrane (CM), and AS1411 aptamer on the gold nanostars (Au@MBN@CM@apt) for synergistic targeted imaging of tumor cells. The Au@MBN@CM@apt probe integrates the distinctive functional properties of its constituent components. The internal gold nanostars (AuNS) with multi-tip structure significantly enhance the signal of Raman reporter molecules. Raman reporter molecule 4-MBN is adsorbed on the surface of AuNS, and its cyano group yields a characteristic Raman peak at 2226 cm^-1, within Raman silent region, thereby minimizing the interference from endogenous biomolecules. Encapsulation with cell membrane endows the nanoprobes with excellent stability and biocompatibility, thus reducing phagocytosis and clearance by macrophages. Moreover, the incorporation of AS1411 aptamers into the cell membrane enables specific recognition of nucleolin, a protein overexpressed in various cancer cell types. With these merits, the designed Au@MBN@CM@apt nanoprobes exhibit distinct SERS signals in the Raman silent region, free from interference by endogenous biomolecules, and maintain good stability, with retained signal stability for up to 170 days. These characteristics render them suitable for the targeted detection and SERS imaging of nucleolin-overexpressing cancer cells, using MCF-7 cells as the model, against normal cells. Furthermore, the Au@MBN@CM@apt nanoprobes generates signals in the Raman silent region, thereby effectively avoiding spectral overlap with intrinsic tissue components. As a result, they were successfully used for SERS imaging of tissue sections, allowing high-contrast delineation of tumor tissue margins with results consistent with hematoxylin and eosin (H&E) staining. Collectively, these findings demonstrate that our work holds significant promise for background-free tumor visualization.