Abstract

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. In vitro and in vivo 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.