Background: Inappropriate macrophages phenotype transition contributes to the development of ulcerative colitis, and the poly (ethylene glycol)-block-poly (d, l-lactic acid) (PEG-PLA) nanoparticles delivery system can be utilized to improve the cryptotanshinone (CTS)-based therapy.

Methods: We used a single emulsification method to prepare CTS-encapsulated nanoparticles (NPCTS). The therapeutic efficacy of NPCTS was evaluated in dextran sulfate sodium (DSS)-induced colitis mice. Then the proportion of total macrophages and M2-like macrophages were assayed with flow cytometry, and the relative content of pro-inflammatory cytokines in the colon was detected with Western blot. Bone-marrow-derived macrophages (BMDMs) were induced into M1-like macrophages, which were further incubated with NPCTS to repolarize into M2 subtype.

Results: Cryptotanshinone could induce the transition of M1 subtype to M2 subtype as indicated by up-regulated expression of arginase 1 (ARG1), interleukin (IL)-10, and CD206. In vivo, orally administrated NPCTS accumulated in the colon-infiltrated macrophages in colitis mice. It further revealed that NPCTS significantly alleviated colitis symptoms as indicated by increased body weight and colon length, decreased tumor necrosis factor (TNF)-α, IL-1β, and IL-6 content in the colon, and diminished total macrophage proportion (CD45+CD11b+F4/80+) and up-regulated M2 proportion (CD45+CD11b+F4/80+CD206hi).

Conclusions: Oral administration of NPCTS could ameliorate ulcerative colitis with the conversion of M1-like macrophages to M2-like macrophages.