Dual-drug loaded phase-changing nanodroplets for image-guided tumor therapy

Phase-changing nanodroplets are sub-micron constructs with perfluorocarbon liquid cores that can be remotely vaporized with optical or acoustic energy to form gaseous microbubbles and expel their contents. This process can generate shock waves, shear forces, and microstreams in the interstitial tumor space, enhancing intratumoral drug delivery1. Furthermore, the resulting microbubbles can act as ultrasound contrast agents, enabling imaging with high sensitivity to guide the delivery of therapeutics. In order to leverage these phenomena for drug co-delivery, we developed lipid-shell nanodroplets (NDs) with a liquid perfluoropentane core by a double emulsion technique. The droplets were loaded with cisplatin and paclitaxel as active agents, as well as indocyanine-green dye to allow for light-triggered drug release and enable photoacoustic imaging2. Both the composition of the shell and of the core emulsion were optimized in order to develop nanoparticles with sizes lower than 300 nm (mean diameter 153 ± 77 nm) to enhance accumulation in tumors. The triggered release of both drugs from the nanodroplets was assessed by laser activation with NIR-light (750 nm). The viability of FaDu cells was used to measure in vitro drug delivery, showcasing the laser triggered release of drugs. The double drug formulation outperformed empty nanodroplets (p= 0.0006), PTX-loaded NDs (p < 0.0001), as well as combinations of paclitaxel and cisplatin in concentrations equivalent to the loaded droplets’ in terms of cell cytotoxicity effects. With these in mind, our long-term goal is to employ the nanodroplets to quantify delivered drug dose, while at the same time minimizing off-target effects. To read more click here