Liposomal Emodin: A nanomedicine for two-photon imaging and mitochondria-targeted photodynamic therapy of psoriasis

Psoriasis is a chronic, immune-mediated inflammatory skin disorder that severely affects patients' life quality due to its persistent nature, high recurrence rate, and limited treatment efficacy. In this study, we develop liposomal emodin (LE) and systematically evaluate its potential for psoriasis diagnosis and therapeutic treatment, particularly through two-photon-excited photodynamic therapy (TPE-PDT). LE demonstrates remarkable transdermal absorption, effectively penetrating psoriatic lesions and significantly alleviating skin inflammation and hyperkeratosis in an imiquimod-induced psoriasis mouse model. Our proteomic and single-cell transcriptomic analyses reveal that LE downregulate macrophage mitochondrial electron transport chain proteins, inhibit inflammatory gene expression, and suppress the activity of inflammatory T cells and fibrosis, thereby improving the immune microenvironment and overall skin pathology. Furthermore, emodin's two-photon excitation properties enhance the imaging depth, enabling high-resolution deep tissue imaging of psoriatic lesions, facilitating precise support for disease diagnosis and therapeutic monitoring. LE also demonstrates significant therapeutic effects by generating reactive oxygen species (ROS) under 800 nm fs pulsed laser, effectively clearing pro-inflammatory cells and regulate the lesion microenvironment. This study introduces an innovative approach for the integrated diagnosis and treatment of psoriasis, paving the way for advanced imaging and precision therapy for complex skin diseases. (A) The preparation procedure of LE. (B) LE plays a role in indicating inflammatory cells and enhancing fluorescence intensity in both mouse and human two-photon imaging. (C) Mechanism of LE in photodynamic therapy for psoriasis in a mouse model: targeting Complex IV in macrophage mitochondria, inducing mitochondrial degradation in macrophages, inhibiting T cell cytokine secretion, suppressing keratinocyte proliferation, and inhibiting fibroblast collagen synthesis.