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 ther...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.展开更多
基金supported by National Natural Science Foundation of China(Nos.52161145410,52373126,and 52303173)the National Natural Science Foundation of China-Iran National Science Foundation joint grant(No.4001987)+1 种基金Beijing University of Chemical Technology-China-Japan Friendship Hospital Biomedical Translational Engineering Research Center Key Projects(No.XK2023-20)the longterm subsidy mechanism from the Ministry of Finance and the Ministry of Education of People's Republic of China.M.-A.S.acknowledges the financial support of the incentive and startersbeurs funds from the University of Groningen,Groningen,The Netherlands.
文摘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.
