Piperazine based pH-responsive cyanine dyes for cancer cell photoacoustic imaging

Novel pH-responsive Cy7.5 dyes bearing various amino groups were developed for cancer cell photoacoustic (PA) imaging. Among structurally diverse dyes, pH-dependent absorption spectral changes were observed for those carrying a diazaalkyl group. DFT calculations and absorbance measurements of the dyes revealed that these spectral changes depended on the electron density of the pH-sensing moiety. The PA spectra of the dyes also changed pH-dependent fashion and were largely consistent with the absorption spectra. In PA imaging experiments with cultured cancer cells, the pH-responsive dyes conjugated with a cancer specific antibody accumulated in cancer cells and changed their PA signals depending on the acidic lysosome pH. Overall, these results demonstrated that pH-responsive Cy7.5 dyes can be useful for detecting cancer, and the elucidated mechanism of the absorption spectral changes could contribute to designing new PA imaging agents.