Phase-change perfluorocarbon nanodroplets enable spatiotemporal control of ultrasound and photoacoustic imaging and therapy.

Phase-change perfluorocarbon nanodroplets (PFCnDs) are submicrometer, liquid-core agents capable of generating strong ultrasound (US) and photoacoustic contrast following external stimulation. This selective vaporization allows site-specific signal generation and facilitates imaging beyond the vascular compartment. The behavior of PFCnDs is determined by a thermodynamic landscape in which Laplace pressure and nucleation kinetics jointly influence vaporization thresholds and post-vaporization outcomes, including persistent gas bubble formation or rapid recondensation. This review summarizes the mechanistic framework underlying acoustic droplet vaporization, optical droplet vaporization, and combined optical-acoustic droplet vaporization of PFCnDs. These phase-change mechanisms are discussed in relation to formulation variables such as perfluorocarbon species, size distribution, shell mechanics, and absorber loading, as well as exposure conditions including acoustic pressure, frequency, pulse structure, and optical fluence. The review further examines how these coupled parameters govern vaporization dynamics, imaging persistence, and associated bioeffects. Imaging applications, including contrast-enhanced US, extravascular and lymphatic imaging, super-resolution, and multiplexed approaches that leverage vaporization-recondensation behavior, are surveyed. Therapeutic applications, such as drug delivery and barrier-opening techniques, are also examined alongside clinical translation priorities, including manufacturing, in vivo fate verification, reproducible vaporization, and standardized safety dosimetry.