Therapeutic Effect of a Novel M1 Macrophage-Targeted Nanodrug in Chronic Periodontitis Mice.

ABSTRACT

Chronic periodontitis is a chronic, progressive, and destructive disease. Especially, the large accumulation of advanced glycation end products (AGEs) in a diseased body will aggravate the periodontal tissue damage, and AGEs induce M1 macrophages. In this project, the novel nanodrugs, glucose-PEG-PLGA@MCC950 (GLU@MCC), are designed to achieve active targeting with the help of glucose transporter 1 (GLUT1) which is highly expressed in M1 macrophages induced by AGEs. Then, the nanodrugs release MCC950, which is a kind of NLRP3 inhibitor. These nanodrugs not only can improve the water solubility of MCC950 but also exhibit superior characteristics, such as small size, stability, innocuity, etc. In vivo experiments showed that GLU@MCC could reduce periodontal tissue damage and inhibit cell apoptosis in periodontitis model mice. In vitro experiments verified that its mechanism of action might be closely related to the inhibition of the NLRP3 inflammatory factor in M1 macrophages. GLU@MCC could effectively reduce the damage to H400 cells caused by AGEs, decrease the expression of NLRP3, and also obviously reduce the M1-type macrophage pro-inflammatory factors such as IL-18, IL-1ß, caspase-1, and TNF-α. Meanwhile, the expression of anti-inflammatory factor Arg-1 in the M2 macrophage was increased. In brief, GLU@MCC would inhibit the expression of inflammatory factor NLRP3 and exert antiperiodontal tissue damage in chronic periodontitis via GLUT1 in the M1 macrophage as the gating target. This study provides a novel nanodrug for chronic periodontitis treatment.