Liquid-gas phase-change nanoplatforms for ultrasound-mediated cancer theranostics

Ultrasound has emerged as a powerful modality for cancer theranostics due to its noninvasiveness, deep-tissue penetration, and real-time feedback. However, the limited stability and short circulation time of traditional microbubble contrast agents restrict their clinical potential. Liquid-gas phase-change nanoplatforms, also known as phase-change contrast agents (PCCAs), offer a promising alternative by enabling acoustic-triggered vaporization of perfluorocarbon (PFC) cores, facilitating enhanced imaging performance and spatiotemporally controlled therapeutic functions. This review introduces the fundamental mechanisms underlying the liquid-gas phase transition, including acoustic cavitation, heating, and radiation force effects. It then summarizes the design strategies for PCCAs, covering PFC core selection (from low- to high-boiling-point types), diverse carrier platforms (lipid-, polymer-, and nanoemulsion-based systems), and surface functionalization approaches for targeted delivery and stimulus responsiveness. Subsequently, the applications of PCCAs in ultrasound-guided cancer theranostics are discussed, encompassing their roles in diagnostic imaging as well as in ultrasound-mediated mono- and combination therapies, such as chemotherapy, phototherapy, and immunotherapy. Finally, the review concludes with current challenges and future perspectives on smart material integration, multimodal imaging, and precision delivery strategies, which will be key to unlocking the full potential of PCCAs in cancer diagnosis and treatment.