An in situ therapeutic vaccine for targeted treatment of ulcerative colitis via induction and maintenance of long-term immune tolerance

Ulcerative colitis (UC) has posed a great threat to global human health. As an autoimmune disease, UC is characterized by immune dysregulation and abnormal colonic inflammation. In this study, we design a therapeutic nanoagent for efficient UC treatment through the induction and maintenance of immune tolerance. The nanoagent, termed MRA@RP, consists of a protective pectin shell and an Arg-Gly-Asp (RGD)-modified mesoporous silica nanoparticle (MSN) core that carries all- trans retinoic acid (ATRA) and rhein (RH). After oral administration, the robust MRA@RP can accumulate in the inflamed colon tissues, efficiently adsorb various intestinal antigens in situ , and alleviate inflammation. Moreover, MRA@RP can restore the population balance of CD4 + T cells and promote the production of immunoglobulin A + memory B cells, which contributes to the development of long-term immune tolerance, resulting in superb therapeutic efficacy. Our results suggest that MRA@RP may overcome the limitations of traditional UC treatment approaches via effective immunoregulation.