Macrophage membrane-biomimetic cinnamaldehyde nanomedicine ameliorates inflammatory bowel disease by suppressing macrophage M1 polarization

Rationale: Presl, has exhibited therapeutic potential for IBD. However, the therapeutic mechanism of CMA remains incompletely elucidated, and clinical translation is hampered by its poor oral pharmacokinetics. Methods: Using RAW 264.7 cells stimulated with either LPS or IL-4, we evaluated the effects of CMA on macrophage polarization. Subsequently, the impact of CMA on glucose metabolism in M1 macrophages was analyzed. RNA sequencing identified the signaling pathways through which CMA inhibits M1 macrophage polarization, and this was further validated through genetic or pharmacological blockade. To overcome the pharmacokinetic challenges of CMA, macrophage membrane-biomimetic CMA-loaded nanoparticles (MM@CMANP) were designed, and their pharmacokinetics and targeting to intestinal inflammation sites were evaluated. Finally, the efficacy of MM@CMANP was assessed in DSS-induced IBD mice. Results: . Conclusions: These results establish mitophagy as a central mechanism underlying anti-IBD effects of CMA and position MM@CMANP as a clinically translatable nanotherapeutic platform for IBD.