Protein Precoating with Concentration-Dependent Manner Breaks through the Biomacromolecular Barrier of Transferrin-Functionalized Nanoparticle in Intestinal Mucosa

Biomacromolecules in physiological environments would adsorb onto the nanoparticles (NPs) to form corona layers, in which protein coronas (PCs) are the major constituent. PCs always play diverse influences on the fate of NPs in vitro and in vivo, especially for active-targeting NPs (e.g., transferrin-modified nanoparticles, Tf-NP). In order to eliminate the inhibition of PCs on the efficiency of Tf-NP, the precoated Tf-NP with bovine serum albumin (BSA, B@Tf-NP) was designed to fabricate an "active PCs" (PCs formed by artificial modification) against the "passive PCs" (PCs formed in the biological environments), which was inspired by the formation pattern of PCs. The results indicated that B@Tf-NP had similar particle size, dispersion, and physical stability with Tf-NP. Surprisingly, B@Tf-NP enhanced the cellular uptake in enterocytes and permeability in intestinal tract of mice. Notably, the concentration ratio of BSA to Tf that could ensure Tf revealed timely during the interacted process was considered to be appropriate. These findings provide an easy while efficient design platform for active-targeting NPs to overcome the biomacromolecular barrier in oral administration.