A Dual-Modal SERS/Fluorescence Gold Nanoparticle Probe for Mitochondrial Imaging

A novel SERS/fluorescent multimodal imaging probe for mitochondria has been synthesised using 12 nm diameter gold nanoparticles (AuNP) surface functionalised with a rhodamine thiol derivative ligand. The normal pH-dependent fluorescence of the rhodamine-based ligand is inversed when it is conjugated with the AuNP and higher emission intensity is observed at basic pH. This switch correlates to a pK_a at pH 6.62, which makes it an ideal candidate for a pH-sensitive imaging probe in the biological range (pH 6.5-7.4). The observed pH sensitivity of the ligand when attached to the AuNP is thought to be due to the formation of a spirolactam ring, going from positively charged (+18 mV) to negatively charged (-60 mV) as the pH is changed from acidic to basic. Additionally, conjugation of the ligand to the AuNP serves to enhance the Raman signal of the rhodamine ligand through surface-enhanced Raman scattering (SERS). Confocal microscopy has shown that the probe enters HEK293 (kidney), A2780 (ovarian cancer) and Min6 (pancreatic beta) cells within an hour and a half incubation time. The probe was shown to localise in the mitochondria, thus providing a novel pH-dependent SERS/fluorescent multimodal imaging probe for mitochondria.