Immunomodulatory copper-doped Houttuynia cordata derived carbon dots enable acute lung injury therapy via near infrared-amplified mitophagy

Abstract Acute lung injury (ALI) is an acute progressive hypoxic respiratory failure driven by various pathogenic factors. The current therapeutic strategies mainly focus on controlling the primary disease, and offering protective support but show limited efficacy in pulmonary repair. Herein, a novel type of novel carbon dot (CC@SS31) was fabricated by hydrothermal reaction of Houttuynia cordata followed by ultra-small copper loading and SS31 modification, which exhibited the various mimetic enzymatic activities. Combining with near infrared (NIR) irradiation, CC@SS31 + NIR had confirmed the enhanced functions of reactive oxygen species (ROS) scavenging, downregulation of inflammatory cytokines, upregulation of anti-inflammatory cytokines as well as promotion of tissue repair factors. In ALI rat models, it had demonstrated that CC@SS31 + NIR could be enriched in the lung, further to alleviate the ROS levels of lung, reduce lung inflammation, and promote the tissue repair with high biosafety. Furthermore, the amplified mitophagy was induced following CC@SS31 + NIR treatment, thereby effectively and precisely promoting the mitochondrial functions repair. Significantly, CC@SS31 + NIR also activated immunoregulation by inducing macrophages M2 polarization, and modulating T cells ratio, thus re-establishing pulmonary immune homeostasis. The work provided a mechanistic foundation for natural derived carbon dots as the multiple functions therapeutic strategies in inflammation related disease. Graphical abstract