Near infrared enhanced palladium loaded siraitia grosvenorii carbon dots amplify mitophagy for acute lung injury immunotherapy

Mitophagy is a self-protection mechanism for cells to eliminate dysfunctional mitochondria, and maintain mitochondrial homeostasis. Thus, precisely inducing mitophagy represents a promising strategy for acute lung injury (ALI) immunotherapy. Here, the mitochondrial targeted palladium loaded siraitia grosvenorii derived carbon dots (CPs@SS31) were engineered designed to integrate PTT, mitophagy induction, and immunoregulation for synergistic enhanced ALI therapy. CPs@SS31 combining with near infrared (NIR) irradiation not only directly scavenged reactive oxygen species to achieve antioxidant and anti-inflammation, but also amplified mitophagy via activating PINK1/Parkin pathway. Furthermore, it specifically targeted mitochondria to increase ATP production and mitochondrial membrane potential, thereby repairing the mitochondrial function of lipopolysaccharide induced cells. Meanwhile, it also demonstrated that CPs@SS31+NIR efficiently induced macrophage M2 polarization, and upregulated CD4⁺ T cells number and CD4⁺/CD8⁺ ratio, thereby activating immunoregulation, and achieving ALI repair therapy. <i>In vitro</i> and <i>in vivo</i> studies both demonstrated the robust alleviated lung inflammation, and accelerated lung tissue repair in ALI rats models. This work proposed an innovative "mitophagy induction-immunoregulation" paradigm, offering a promising strategy for ALI therapy, and being extended to the treatment of other inflammation related diseases.