Protein Coronas
Derived from Mucus Act as Both Spear
and Shield to Regulate Transferrin Functionalized Nanoparticle Transcellular
Transport in Enterocytes
posted on 2024-02-28, 22:30authored byDan Yang, Yuqi Feng, Ying Yuan, Linxuan Zhang, Yao Zhou, Adam C. Midgley, Yanrong Wang, Ning Liu, Guoliang Li, Xiaolin Yao, Dechun Liu
The epithelial mucosa is a key biological barrier faced
by gastrointestinal,
intraoral, intranasal, ocular, and vaginal drug delivery. Ligand-modified
nanoparticles demonstrate excellent ability on this process, but their
efficacy is diminished by the formation of protein coronas (PCs) when
they interact with biological matrices. PCs are broadly implicated
in affecting the fate of NPs in vivo and in vitro, yet few studies
have investigated PCs formed during interactions of NPs with the epithelial
mucosa, especially mucus. In this study, we constructed transferrin
modified NPs (Tf-NPs) as a model and explored the mechanisms and effects
that epithelial mucosa had on PCs formation and the subsequent impact
on the transcellular transport of Tf-NPs. In mucus-secreting cells,
Tf-NPs adsorbed more proteins from the mucus layers, which masked,
displaced, and dampened the active targeting effects of Tf-NPs, thereby
weakening endocytosis and transcellular transport efficiencies. In
mucus-free cells, Tf-NPs adsorbed more proteins during intracellular
trafficking, which enhanced transcytosis related functions. Inspired
by soft coronas and artificial biomimetic membranes, we used mucin
as an “active PC” to precoat Tf-NPs (M@Tf-NPs), which
limited the negative impacts of “passive PCs” formed
during interface with the epithelial mucosa and improved favorable
routes of endocytosis. M@Tf-NPs adsorbed more proteins associated
with endoplasmic reticulum-Golgi functions, prompting enhanced intracellular
transport and exocytosis. In summary, mucus shielded against the absorption
of Tf-NPs, but also could be employed as a spear to break through
the epithelial mucosa barrier. These findings offer a theoretical
foundation and design platform to enhance the efficiency of oral-administered
nanomedicines.