Nanoparticles mediated cryosurgery was recently established as an efficient way to significantly improve the output of a conventional freezing therapy. To further improve this newly emerging nanomedicine way for ablating target tumor, here the ultrasound preprocessing was proposed for the first time to enhance the freezing strength to a better level on the tissues. In vitro experiments were carried out to evaluate the effects of a single ultrasound preprocessing, a single nanoparticle loading or their combination in enhancing the cryosurgery. Meanwhile, the mechanisms of the ultrasound preprocessing to improve nanoparticles’ mediated freezing capability were also theoretically interpreted. Experimental measurements demonstrate that, the ultrasound preprocessing on the target tissue site injected with nanoparticles not only evidently expended the freezing area, but also helps realize a much lower temperature scale and offers higher freezing rate during the nanocryosurgical process. Two main reasons to contribute to such effects were identified as the enhanced convective heat transfer in micro scale and the varied cellular impermeability caused by the ultrasound. The combined effect of ultrasound preprocessing and nanoparticles would be greater than the sum of their individual effects in mediating the nanocryosurgery. As a convinced approach, the present method opens a new way for the improved freezing ablation on tumor which can possibly be used in future clinics.

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