Polydopamine Nanoparticle‐Mediated Dopaminergic Immunoregulation in Colitis

Abstract

Despite immunosuppression is critical for reducing immune overactivation, existing immunosuppressive agents are largely restricted by low inhibition efficiencies and unpredictable off-target toxicities. Here, the use of the dopaminergic system is reported to suppress hyperactive immune responses in local inflamed tissues. A polydopamine nanoparticular immunosuppressant (PDNI) is synthesized to stimulate regulatory T (Treg) cells and directly inhibit T helper 1 (Th1), Th2, and Th17 cells. Moreover, PDNI can inhibit the activation of dendritic cells to upregulate the ratio of Treg/Th17, which assists the reversion of inflammatory responses. The application of dopaminergic immunoregulation is further disclosed by combining with gut microbiota modulation for treating inflammations. The combination is implemented by coating living beneficial bacteria with PDNI. Following oral delivery, coated bacteria not only suppress the hyperactive immune responses but also positively modulate the gut microbiome in mice characterized with colitis. Strikingly, the combination demonstrates enhanced treatment efficacies in comparison with clinical aminosalicylic acid in two murine models of colitis. The use of the dopaminergic system opens a window to intervene immune responses and provides a versatile platform for the development of new therapeutics for treating inflammatory diseases.

Dimethylamino group modified polydopamine nanoparticles with positive charges to scavenge cell-free DNA for rheumatoid arthritis therapy

“…PDA and its derivatives also had potential scavenging effects on excessive reactive oxidative stress (ROS), further alleviating and treating ROS derived diseases such as ischemic stroke, Parkinson and osteoarthritis due to its abundant reductive groups like catechol and imine [ [24] , [25] , [26] , [27] ]. PDAs tended to target dopamine receptors, which were highly expressed in immune diseases including RA, and functions as immune system regulator as well [ 28 ]. Significantly, it had unique property of bioadhesion similar to mussel-adhesive proteins that displayed high adhesion to most substrates [ 29 ].…”

Engineered probiotics

“…This self-regulating engineered yeast probiotic inhibits intestinal inflammation and reduces intestinal fibrosis and dysbiosis in IBD mouse models and we think their self-regulating strategy may provide a new way for engineered probiotics to treat IBD or other diseases. Liu Jinyao's team at Shanghai Jiaotong University School of Medicine in China synthesized a polydopamine nano immunosuppressant and used it to coat E. coli Nissle 1917 to inhibit the excessive immune response in the local tissues of mouse colitis and regulate the intestinal microbiota to promote the reversal of inflammation [ 21 ]. Liu et al's study showed that applying immunosuppressants on the surface of beneficial bacteria can promote improved colitis responses in mice.…”

Gpr174 Knockout Alleviates DSS-Induced Colitis via Regulating the Immune Function of Dendritic Cells

“…Recent studies demonstrated that the immune imbalance between CD4 + T cells, Th1/Th2, and Treg might be the most direct and vital factor in the pathogenesis of IBD. It also played a role in mediating the occurrence of ulcerative colitis ( 34 , 35 ). The current study suggested a reducing ratio of Th1/Th2 and Treg in LP alleviated inflammatory response in colonic tissue.…”