Production of multi-scale fluorocarbon droplets mediated by microwave-induced thermal phase transition and its synergistic efficacy of microwave ablation / 中华超声影像学杂志

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.

Experimental study of a novel phase change nanodroplets enhanced high intensity focused ultrasound ablation / 中国介入影像与治疗学

Objective To investigate the effect of lipid encapsulated 1,1,2-trichlorotrifluoroethane phase change nanodroplets for high intensity focused ultrasound (HIFU) ablation.Methods The lipid encapsulated 1,1,2-trichlorotrifluoroethane phase change nanodroplets was prepared with membrane hydration method,and its physicochemical properties were examined.The synergistic effect of HIFU ablation was verified with experiments in vitro and in vivo experiments.For in vitro experiment,the isolated bovine liver tissues were irradiated with HIFU (250 W,10 s,continuous wave).For in vivo experiment,the livers of New Zealand rabbits were irradiated with HIFU (200 W,5 s,continuous wave).The volume of coagulative necrosis,energy efficiency factors (EEF) and the volume of the hyperechoic area after HIFU radiation were measured.And the statistical analysis was performed.Results Phase change nanoparticles were spherical in solution and uniform in size.For in vitro experiment,the coagulative necrosis volume,EEF and hyperechoic area of bovine liver tissue injected with nanodroplets were significantly higher than those of untreated bovine liver tissue (t=28.80,19.55,14.30;P=0.01,0.02,0.02) after HIFU.For in vivo experiment,the coagulative necrosis volume,EEF and hyperechoic area of rabbit liver tissue injected with nanodroplets were significantly higher than those of untreated rabbit liver tissue (t=9.41,13.52,15.67;P=0.02,0.01,0.01) after HIFU.Conclusion The lipid encapsulated 1,1,2-trichlorotrifluoroethane phase change nanodroplets can significantly improve the efficiency of HIFU ablation significantly.

Development of Ultrasound Sensitive eLiposomes Containing Doxorubicin for Drug Delivery.

Aims: A novel nanocarrier was formulated by remote loading of doxorubicin (Dox) into a dipalmitoylphosphatidylcholine (DPPC) liposome that also contains various perfluorocarbon (PFC) droplets within its aqueous interior. It was shown that Dox can be loaded to a level of up to 67% into these large unilamellar vesicles composed of DPPC and cholesterol by employing a transmembrane pH gradient technique. Methods: The different encapsulation efficiencies for these eLipoDox constructs of differing PFC composition are 45.5% (PFC5), 31.5% (PFC6) and 66.7% (PFC5/PFC6 mixture, PFCm). At 30 seconds of insonation, the eLipoDox formulation with PFCm droplets appeared to release more Dox than did eLipoDox with pure PFC5 or PFC6 droplets. The thermal stability of these eLipoDox formulations were examined at 37°C at different times; then controlled delivery was demonstrated by applying low-frequency ultrasound (US) at 1 W/cm2. Results: The eLipoDox with PFC6 or PFCm showed the best combination of thermal stability and drug release. An immunoblotting analysis indicates that ultrasound-triggered Dox release from eLipoDox could provide a higher quantity of nanodrug into tumor cells and thus may have cytostatic effects in cancer cells. Conclusion: These eLipoDox constructs with low boiling point PFCs have the potential to provide more effective ultrasonically activated drug therapy to a desired location.