Objective:To explore the mechanism of phase-transition fluorocarbon nanomaterials and evaluate its synergistic efficacy on microwave ablation (MWA).Methods:A novel phase transition nanodroplet (PTN) was designed with poly (lactic-co-glycolic acid) (PLGA) as the shell and perfluorocarbon (PFC) mixture as the core. Based on that, a phase-transition mechanism of microwave droplet vaporization (MWDV) was explored, which was based on the thermal phased transition. The basic physicochemical properties and biological characteristics of PTN were monitored by scanning electron microscope (SEM), dynamic laser light scattering (DLS), in vitro hemolysis and CCK-8 experiment.Based on the gel-hole model experiment in vitro, the phase transition of PTN were monitored; based on the live/dead cell double staining kit, flow cytometry and cytotoxicity test, the synergistic efficacy of phase-transition PTN on microwave ablation, which was mediated by MWDV was evaluated. Results:The phase-transition temperature of PTN was exactly the boundary temperature of microwave ablation (60 ℃) when the ratio between perfluoropentane (PFP) and perfluorohexane (PFH) in the core of PTN was 3∶2. Furthermore, the smart proportional PTN didn′t only have good stability and biocompatibility, but also could enhance the two-dimensional ultrasonic imaging and increase the efficacy of MWA under the mediation of MWDV.Conclusions:MWDV can be treated as a phase-transition mechanism of fluorocarbon nanomaterials, which provides a potential synergistic strategy for the thermal ablation of tumors.