Photothermal-triggered oxygen-releasing nanodroplets for oral cancer therapy associated with NF-κB signaling modulation and antibacterial effects

Tumor hypoxia and intratumoral bacterial colonization can limit the therapeutic efficacy in oral squamous cell carcinoma (OSCC). Here, we developed an oxygen-carrying multifunctional nanodroplet, Cs x WO 3 @PFC (CsWO@PFC), assembled from the photothermal agent Cs x WO 3 , the oxygen carrier perfluorocarbon (PFC), and human serum albumin (HSA). The formulation was oxygenated immediately before administration and delivered by in situ intratumoral injection into tumors established in the right lower lip of BALB/c nude mice. Under 1064 nm laser irradiation, rapid photothermal heating induced an irradiation-associated improvement in tumor oxygenation, consistent with the oxygen-carrying property of thePFC componentand alleviation of tumor hypoxia. In parallel, the treatment was associated with enhanced singlet oxygen ( 1 O 2 ) generation under 1064 nm laser irradiation, leading to improved tumor therapeutic effects. Histological and molecular analyses showed increased γH2AX, reduced proliferative activity, and apoptosis-associated marker changes. Treatment-related NF-κB signaling modulation was also observed, including reduced p65 phosphorylation and shifts in pro- and anti-apoptotic protein expression. Meanwhile, the treatment reduced intratumoral bacterial burden and inhibited tumor growth in bacteria-colonized OSCC mouse models. Collectively, these findings support the therapeutic potential of CsWO@PFC-mediated PTT/PDT treatment for bacteria-colonized oral malignancies.