Modulation of photoacoustic NIR BODIPY self-assembly in theranostic solid lipid nanoparticles via alpha-group variation: influence on spectral and nanostructural properties†

Loading drug nanovectors with a high quantity of near-infrared organic dye considerably increases their absorption cross-section and favors their detection as theranostic agents with photoacoustic imaging. In a previous study, solid lipid nanoparticles (SLNs) of dexamethasone palmitate were labeled with BODIPY–aniline–palmitate and revealed exquisite photoacoustic properties: a NIR absorption cross-section comparable to gold nanoparticles and a photoacoustic generation efficiency above 1. However, strong and gradual spectral modifications were observed with the increasing dye concentration. The spectral transformations were linked to dye aggregation in the SLNs, and potential further transformations occuring after in vivo injection may hinder longitudinal imaging applications. In the present study, we introduce BODIPY–julolidine–palmitate, a second dye able to label the SLNs, but without any marked aggregation behaviour. We perform a comparative study of labelled SLNs in various matching concentrations of each dye in terms of optical and photoacoustic properties, showing lower modifications of the spectral behaviour with the dye concentration for BODIPY–judolidine and establishing the influence of the lipid core on the photoacoustic generation efficiency regardless of the dye. Cryo-EM and SAXS–WAXS studies reveal a lamellar arrangement at the nanoscale for SLNs labelled with a high concentration of BODIPY–aniline whereas SLNs labelled with BODIPY–julolidine display an amorphous structure. Overall, BODIPY–julolidine–palmitate at moderate label concentration appears a better candidate to label SLNs for theranostic applications using photoacoustic imaging.