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Dui Qin,1,2,* Lei Zhang,1,* Hongrui Zhu,1 Junjie Chen,1 Daocheng Wu,1 Ayache Bouakaz,3 Mingxi Wan,1 Yi Feng1 1The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an, People’s Republic of China; 2Department of Biomedical Engineering, School of Bioinformatics, Chongqing University of Posts and Telecommunications, Chongqing, People’s Republic of China; 3UMR 1253, iBrain, Université de Tours, Inserm, Tours, F-37032, France*These authors contributed equally to this workCorrespondence: Mingxi Wan; Yi FengThe Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi’ an Jiaotong University, Xi’ An, 710049, People’s Republic of ChinaTel +86 29 82667924Fax +86 29 82668668Email mxwan@mail.xjtu.edu.cn; fengyi@mail.xjtu.edu.cnBackground: Photothermal therapy (PTT) has attracted considerable attention for cancer treatment as it is highly controllable and minimally invasive. Various multifunctional nanosystems have been fabricated in an “all-in-one” form to guide and enhance PTT by integrating imaging and therapeutic functions. However, the complex fabrication of nanosystems and their high cost limit its clinical translation.Materials and Methods: Herein, a high efficient “one-for-all” nanodroplet with a simple composition but owning multiple capabilities was developed to achieve ultrasound (US) imaging-guided and cavitation-enhanced PTT. Perfluoropentane (PFP) nanodroplet with a polypyrrole (PPy) shell (PFP@PPy nanodroplet) was synthesized via ultrasonic emulsification and in situ oxidative polymerization. After characterization of the morphology, its photothermal effect, phase transition performance, as well as its capabilities of enhancing US imaging and acoustic cavitation were examined. Moreover, the antitumor efficacy of the combined therapy with PTT and acoustic cavitation via the PFP@PPy nanodroplets was studied both in vitro and in vivo.Results: The nanodroplets exhibited good stability, high biocompatibility, broad optical absorption over the visible and near-infrared (NIR) range, excellent photothermal conversion with an efficiency of 60.1% and activatable liquid-gas phase transition performance. Upon NIR laser and US irradiation, the phase transition of PFP cores into microbubbles significantly enhanced US imaging and acoustic cavitation both in vitro and in vivo. More importantly, the acoustic cavitation enhanced significantly the antitumor efficacy of PTT as compared to PTT alone thanks to the cavitation-mediated cell destruction, which demonstrated a substantial increase in cell detachment, 81.1% cell death in vitro and 99.5% tumor inhibition in vivo.Conclusion: The PFP@PPy nanodroplet as a “one-for-all” theranostic agent achieved highly efficient US imaging-guided and cavitation-enhanced cancer therapy, and has considerable potential to provide cancer theranostics in the future.Keywords: one-for-all nanodroplet, theranostics, photothermal therapy, acoustic cavitation, ultrasound imaging