Nano-photosensitizer loaded with salvianolic acid B and ALA enhances the efficacy of photodynamic therapy for oral leukoplakia

5-aminolevulinic acid (ALA) photodynamic therapy (PDT), a non-invasive approach for oral leukoplakia, is limited by hypoxia in the lesion microenvironment. A novel nano-photosensitizer incorporating salvianolic acid B (SalB) and ALA (nano-SalB-ALA) has been shown to enhance PDT effect by reliving hypoxia. We optimized the concentration ratio of SalB and ALA (nano-SalB10-ALA250) using cell viability and live/dead staining assays. Cellular uptake was confirmed via confocal laser scanning microscopy, and an animal model of tongue leukoplakia was established to assess in vivo PDT effects. Nano-SalB10-ALA250 reversed glucose metabolic reprogramming linked to the PI3K/AKT/mTOR pathway and scavenged abnormal reactive oxygen species accumulation in vitro and in vivo, thereby enhancing the effect of PDT on oral leukoplakia. Nano-SalB10-ALA250 significantly enhances PDT efficacy for oral leukoplakia, offering a potential clinical application for improved treatment outcomes.