Light-activated doxorubicin-encapsulated perfluorocarbon nanodroplets for on-demand drug delivery in an in vitro angiogenesis model: Comparison between perfluoropentane and perfluorohexane.

Phase-transition perfluorocarbon (PFC) nanodroplets have been developed for on-demand drug delivery carriers with external triggers such as ultrasound or laser irradiation techniques. Although various perfluorocarbons, including perfluoropentane (C5F12) and perfluorohexane (C6F14), have been investigated for their theranostic use, comparison of the phase-transition efficiency, the drug delivery efficacy by light activation, and physical properties of the PFC nanodroplets have not been reported. We have synthesized gold nanorod-coated doxorubicin-encapsulated perfluorocarbon nanodroplets using perfluoropentane and perfluorohexane as light-activated on-demand drug delivery carriers, called PF5 and PF6, respectively. When gold nanorods on the perfluorocarbon nanodroplets resonate with a laser wavelength, plasmonic heat generated on the gold nanorods vaporizes the nanodroplets to gas bubbles (phase-transition), and releases the encapsulated drug from the nanodroplet core. Overall, the nanodroplet size, drug encapsulation efficiency, number density, and cytotoxicity were similar between PF5 and PF6. However, the long-term stability against passive phase-transition or coalescence in physiological conditions and the phase-transition efficiency were different from each other. PF6 was better in long-term stability but showed lower phase-transition than PF5. The lower phase-transition of PF6 might have led to lower drug delivery efficiency compared to PF5. This is probably because PF6 has higher temperature thresholds required for phase-transition due to its higher boiling point. The study demonstrated feasibility of the light-activated nanodroplets for on-demand targeted nanotherapy, which suppresses the development of angiogenesis.