Phase-change nano-droplets (PCNDs) have been gaining attention for their potential applications in ultrasound-based therapeutic and diagnostic technologies. PCNDs transform from a droplet state to microbubbles in response to ultrasound or shockwaves. Although a negative pressure component contributes to this vaporization, previous studies have primarily used ultrasound with both positive and negative pressure components. Thus, the effect of the negative pressure component has not been sufficiently explored. In this study, we developed an experimental system that generates a negative pressure component using underwater shockwaves reflected at the water-air interface. Using PCNDs composed of perfluorohexane (PFH) with a boiling temperature of 59℃, we analyzed the bubble lifetime, response to pressure, and vaporization threshold when exposed to reflected waves with a rise time of 50 ns. The results showed a bubble lifetime of 11 μs, a linear response to negative peak pressure, and a threshold of vaporization between 1.5 MPa and 1.9 MPa. Moreover, the effects of vaporization of PCNDs on biological cells were evaluated by measuring cell viability before and after exposure to negative pressure.