Background: Phase-change nanodroplets (PCNDs), which are liquid perfluorocarbon nanoparticles, have garnered much attention as ultrasound-responsive nanomedicines. The vaporization phenomenon has been employed to treat tumors mechanically. However, the ultrasound pressure applied to induce vaporization must be low to avoid damage to nontarget tissues.
Aims: Here, we report that the pressure threshold for vaporization to induce cytotoxicity can be significantly reduced by selective intracellular delivery of PCNDs into targeted tumors.
Methods and results: In vitro experiments revealed that selective intracellular delivery of PCNDs induced PCND aggregation specifically inside the targeted cells. This close-packed configuration decreased the pressure threshold for vaporization to induce cytotoxicity. Moreover, following ultrasound exposure, significant decrease was observed in the viability of cells that incorporated PCNDs (35%) but not in the viability of cells that did not incorporate PCNDs (88%).
Conclusions: Intracellular delivery of PCNDs reduced ultrasound pressure applied for vaporization to induce cytotoxicity. Confocal laser scanning microscopy and flow cytometry revealed that prolonged PCND-cell incubation increased PCND uptake and aggregation. This aggregation effect might have contributed to the cytotoxicity threshold reduction effect.
Keywords: acoustic droplet vaporization; intracellular vaporization; perfluorocarbon; phase‐change nanodroplets; stimuli‐responsive materials; ultrasound.
© 2019 Wiley Periodicals, Inc.