A GaPPIX-based ultrasound-responsive phase-change nanodroplet for coordinated antibacterial and sono-chemo therapy of breast cancer

Intratumoral bacteria such as Fusobacterium nucleatum have been increasingly recognized as modulators of tumor progression and therapeutic resistance, motivating localized and antibiotic-free strategies for targeting tumor-colonizing bacteria. Herein, we developed an ultrasound-responsive liposomal nanodroplet (LPGD) co-loaded with gallium protoporphyrin IX (GaPPIX), doxorubicin (DOX), and perfluorohexane (PFH) for the coordinated treatment of F. nucleatum -colonized breast tumors. In this study, GaPPIX served as an antibiotic-free dual-functional agent for both intratumoral bacterial eradication and ultrasound-activated tumor inhibition, while PFH endowed the nanodroplets with phase-transition-enhanced payload release and local intratumoral distribution under ultrasound irradiation. As a result, LPGD exhibited favorable ultrasound responsiveness, potent antibacterial activity, and enhanced antitumor efficacy both in vitro and in vivo . Overall, this work provides an antibiotic-free and ultrasound-amplified strategy for coordinated elimination of intratumoral bacteria and suppression of tumor, offering a promising approach for the treatment of F. nucleatum -associated breast tumors.