SERS analysis of carcinoma-associated fibroblasts in a tumor microenvironment based on targeted 2D nanosheets

Carcinoma-associated fibroblasts (CAFs), one of the most important components of a tumor microenvironment (TME), play a significant role in the complex tumorigenesis process. Herein, the evolution of CAFs in TME is elaborately investigated by surface-enhanced Raman spectroscopy (SERS), a molecular fingerprint technique. Two-dimensional (2D) nanocomposites consisting of gold nanoparticles and a supramolecular "PCsheet" self-assembled between 2D nanosheets and oxidized phosphatidylcholine (PC) are fabricated as SERS-active probes to specifically recognize the CD36 receptor on the cytomembrane of the fibroblasts, a reliable landmark of CAF development. The 2D SERS substrates can also illuminate the fingerprint information around the CD36 protein with high detection sensitivity, which helps elucidate the biochemical component transition in the protein mini-domain during carcinoma progression. Visualized data are then supplied by label-free SERS imaging to exploit the distribution of biomolecules on the plasma membrane. In addition, the repressed expression of CD36 in TME is detected in lung metastasis tumor-bearing mice. This study based on the 2D SERS technique opens up an alternative avenue for unveiling carcinoma-associated molecular events.