Optically Activatable Double-Drug-Loaded Perfluorocarbon Nanodroplets for On-Demand Image-Guided Drug Delivery

Phase-changing nanodroplets have been studied as externally activatable in situ microbubble precursors. The nanodroplets can be triggered to vaporize with an external optical or acoustic energy source, and the resulting microbubbles can be visualized with high sensitivity using ultrasound imaging. Because of their nanoscale size, this type of construct is attractive for the encapsulation and on-site, on-demand release of therapeutics. Here, we develop a double-drug loaded nanodroplet platform that can coencapsulate paclitaxel and doxorubicin, and release them upon external laser activation. Nanodroplets are characterized in terms of size, stability, protein interaction, and drug release. Their capacity to concurrently release the two drugs and generate ultrasound contrast is demonstrated in vitro. The efficacy of dual-drug loaded nanodroplets is compared in vitro with that of free drug formulations, and potential mechanisms of their enhanced cytotoxic behavior are explored. Overall, the results show that the nanodroplets are a versatile platform for on-demand image-guided drug delivery.