Fluorescent organic ion pairs based on berberine: counter-ion effect on the formation of particles and on the uptake by colon cancer cellsElectronic supplementary information (ESI) available: Volumes and concentrations of solutions used to prepare Ber+X− salts using Protocol 1, solid-state spectroscopic characteristics of the berberine salts, UV-vis absorption spectra of berberine salts in acetonitrile, water and Opti-MEM, transmission electron microscopy images, toxicity test for Ber+Pal−, micr

Four organic salts of berberine, a natural alkaloid, were prepared, characterized and studied for their fluorescence properties in solution and in the solid state. Aqueous suspensions of salt-based nanoparticles (NPs) were generated using the ion association technique. The amount and size of the formed NPs were examined by UV-vis absorption spectroscopy, dynamic light scattering and transmission electron microscopy. They were closely dependent upon the nature of the salt and the experimental conditions of preparation. For instance, the four organic salts formed NPs in water, while only the tetraphenylborate salt (Ber + TPB − ) was shown to give stable particles in the cell culture medium, i.e. Opti-MEM supplemented by fetal calf serum. The behaviour of these salts placed in contact with cells was investigated. All berberine salts entered the cells and were detected in the reticulum and mitochondria. However, the cell fluorescence was much stronger for Ber + TPB − than for the other salts. It could not be ascertained whether this effect was attributable to the intrinsic chemical properties of the Ber + TPB − salt or to the presence of nanoparticles. The nature of the anion also influenced the dye diffusion within the cells under illumination. A strong phototoxic effect was observed. This study showed the interest of using organic salts for improved uptake of active compounds, and underlined the potential of carrier-free nano- and submicrometric particles for therapy, phototherapy and diagnosis. Counter-ions modulate the fluorescence of berberine ion pairs in cells, this process being possibly linked to the formation of nanoparticles.