Quantification of doping state of redox sensitive nanoparticles for probing the invasiveness of cancer cells using surface enhanced Raman scattering

Redox activity is known to regulate migration, invasion, metastasis, proliferation, and vascularization of cancer. Because cancer is heterogeneous, the role of redox activity in different cancers and cancer-related processes vary widely. In this study, water soluble, Tween 80-coated polyaniline (TPAni) nanoparticles were synthesized and used as nano-agents for sensing the redox activities of various cancer cells. To identify the relationship between the redox activity and the aggressiveness of cancer cells, two different cancer cell lines, derived from the same tissue but different with regards to aggressiveness, were selected for study. First, the cancer cell lines were incubated with TPAni nanoparticles, and an absorbance ratio obtained from the cell culture media was used as a colorimetric indicator of the redox activities of the cells. Simultaneously, hydrophobically modified filter papers coated with silver nanosnowflakes (SNSF) were used as sensing substrates for surface enhanced Raman scattering (SERS). SERS spectra obtained from varying concentrations of rhodamine 6G were used to confirm the detection limit of the SNSF-based SERS substrate. Cell culture media containing TPAni nanoparticles were treated with the SNSF-containing SERS substrates to examine the redox activities of the various cancer cell lines.The redox activities of cancer cell lines were confirmed by absorbance spectral analysis, and these redox activities were better identified via an SERS analysis method. A SNSF-containing SERS substrate, fabricated from SNSF and filter paper, was used to sense redox activity in cancer cell lines and to further identify correlations between redox activity and cancer cell line aggressiveness, as indicated by the use of EpCAM as a biomarker. Finally, potential of ​in vivo ​redox activity sensing was also confirmed.