Dual-functional microneedle with programmatic regulation of macrophage for autoimmune psoriasis treatment
Graphical Abstract
Abstract
Modulating the immune microenvironment to establish sustained positive feedback within immune pathways represents a promising avenue for the treatment of autoimmunity. However, the precise and efficient delivery of therapeutic systems to the subcutaneous basal layer to modulate immune disorders is a major challenge in the treatment of autoimmune psoriasis. In this project, we introduce a dual-functional microneedle (DF-MN) designed to combine MNs with multiple release kinetics and immunotherapy, the programmed treatment is achieved through segmented design of the MN structure, realizing the unification of rapid and long-lasting treatment of autoimmune psoriasis. In vivo imaging results showed that GelMA@M-CSF showed fluorescent signals after 5 days of delivery to subcutaneous tissues, whereas HA@IL-13 showed minimal fluorescent signals after 2 days. The multistage release behavior of MNs and the diffusion mechanism of drugs were explained at the molecular level, in combination with coarse-grained molecular dynamics. Additionally, DF-MN can successfully induce macrophage reprogramming in vitro and ameliorate overall symptoms in a psoriasis mice model, suggesting that it has the potential to be an effective strategy for the treatment of psoriasis and portends to be a transformative platform for the treatment of other autoimmune diseases.
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References
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