cRGD peptide incorporated with patchouli alcohol loaded silk fibroin nanoparticles for enhanced targeting of inflammatory sites in colitis.

The combination therapy of strengthening inflammation regression and mucosal repair may overcome the "therapeutic ceiling" of ulcerative colitis (UC). However, poor targeting is an outstanding challenge in the preparation of drug delivery systems for UC treatment. Here, we developed anti-inflammatory drug (patchouli alcohol, PA)-loaded nanoparticles (NPs) derived from natural silk fibroin (SF) and subjected to surface functionalization with cyclo RGD peptide (cRGD). Self-assembled SF NPs realized sustained drug release. Meanwhile, cRGD functionalization yielded notably targeted drug delivery to inflamed colon, and thereby enhanced the anti-inflammatory and barrier repair capabilities of NPs. Moreover, cRGD-PASFNs regulated innate immune responses and exerted a potent therapeutic efficacy against acute colitis. Surprisingly, the cRGD-PASFNs also modulated the abnormal level of amino acids which are crucial to the integrity of the intestinal barrier. Additionally, oral delivery of this nanomedicine displayed an excellent safety profile in the mouse model. This study confers confidence for the further development of targeted precision therapy for UC and other inflammatory diseases.