Ruthenium polypyridyl squalene derivative: a novel self-assembling lipophilic probe for cellular imaging.

ABSTRACT

Transition metal complexes provide a promising avenue for designing new therapeutic and diagnostic agents. In particular, ruthenium(II) polypyridyl complexes are useful for studying cellular uptake, due to their easy synthesis and unique photophysical properties. Dyes are frequently combined with material substrates to modulate their properties, enhance stability, reduce toxicity, and improve delivery. A novel Ru polypyridyl complex linked to a derivative of the natural lipid squalene (Ru-BIPPBI-hx-SQ) is described. Using the solvent displacement method, Ru-BIPPBI-hx-SQ easily self-assembles into nanosized aggregates in aqueous solution, as characterized by dynamic light scattering. The nanoassemblies exhibit long-lived and intense luminescence. Preliminary biological assessment showed them to be non-toxic; they are efficiently and rapidly transported across the cell membrane without requiring its permeabilization. Ru-labeled nanoassemblies are likely to be significant cellular-imaging tools, probing cellular events at very low concentrations. Moreover co-nanoassembly, with drug-derivatives based on squalenoylation technology, including gemcitabine and paclitaxel, has given interesting preliminary results.