Au@Ag nanoparticles as joint substrate for SERS and SALDI-MS multimodal imaging of cancerous tissues

Metallic nanoparticles (NPs) are used in mass spectrometry imaging (MSI) as substrate for desorption/ionisation of analytes (SALDI-MS). They provide untargeted information about the small molecules content of tumors which can unreveal its subtype, or predicts its response to therapy. NPs can be used in Raman spectroscopy to design SERS nanoprobes (NP covered by a Raman-active molecule, and functionalized by a targeting molecule): combined with Raman micro-imaging, they can localize and/or quantify a biological target such as a cellular membrane receptor to monitor its expression in tissues (linked to tumor evolution and survival). Developing a multimodal imaging methodology based on SERS nanoprobes and untargeted SALDI-MS, and using metallic NPs as joint substrate, could provide local information both on the receptor status and on the tumor chemical composition. We synthesized gold@silver core@shell NPs (Au@Ag) which enable a fine optical properties tuning by controlling the silver shell thickness, leading to simultaneous high UV absorption needed for SALDI and high Raman enhancement factors in the visible range needed for SERS. We used the NPs to synthesize Folate-targeted nanoprobes in the SERS imaging approach to evaluate the expression of Folate Receptor alpha (FRα), an indicator of patient survival, in cancerous tissues. The same bare NPs were used in SALDI-MS imaging to investigate the small molecules content of adjacent tissue slides.
SERS imaging. Following the SERS intensity on the tissue slide allowed us to highlight higher SERS intensities in the tumor region from the ovary samples. We could perform imaging experiments at the tissue scale down to the cellular scale owing to the high spatial resolution offered by Raman Spectroscopy.
SALDI-MS imaging. Discriminative m/z analysis was performed and ROC curves were calculated to highlight m/z values that discriminate the tumor and healthy areas. 11 specific ions are more intense in the tumor than in the healthy part and 4 ions were found more intense in the healthy than in the tumor area. By combining the two techniques, complementary information about ovarian tumors could be obtained.