Dual-Optimized Surface Hydrophobicity and Rigidity Determines Protein Corona Absorption and Composition on Orally Delivered Nanoparticles Treating Colitis

ABSTRACT: Disease-specific protein corona adsorbed on nanocarriers critically determines their in vivo delivery efficiency. Given that macrophages can orchestrate inflammation resolution and mucosa repair, they are regarded as promising therapeutic targets in colitis. Here, we reveal that by altering the physicochemical properties of nanocarriers, we can manipulate the amount and composition of colitis-specific intestinal protein corona (C-IPC) specifically formed on orally administered nanoparticles (NPs), thereby improving colon macrophage targeting and colitis therapy. We demonstrate that increasing surface hydrophobicity of NPs boosts overall protein adsorption during C-IPC formation, leading to improved colon macrophage delivery and colitis therapeutic efficacy of high hydrophobic NPs (Phobic) loaded with budesonide. Moreover, further increasing the rigidity of Phobic can selectively enrich the corona with key macrophage-targeting related proteins, notably S100A8. This dual-optimized hydrophobicity-rigidity co-modulation approach generates an optimal C-IPC characterized by both high protein amount and a high proportion of targeting proteins. Benefiting from it, Phobic with high rigidity (Hard) further promoted the macrophage targeted drug delivery, thus more effectively attenuating the inflammation and restoring the immune homeostasis in male colitis rats. Our work develops a rational strategy of manipulating the disease-specific protein corona formation through multiple-physicochemical properties co-modulation for efficient drug delivery, holding broad promise for diverse nanocarriers and pathologies.

INSTRUMENT(S):

ORGANISM(S): Rattus Norvegicus (rat)

TISSUE(S): Colon

SUBMITTER: Wenbo Cheng  

LAB HEAD: Mingjie Ni

PROVIDER: PXD071116 | Pride | 2026-01-21

REPOSITORIES: Pride