Multifunctional Nanoparticles Enable Efficient Oral Delivery of Biomacromolecules via Improving Payload Stability and Regulating the Transcytosis Pathway

In oral delivery of biomacromolecules, ligand-modified nanoparticles (NPs) have emerged as a promising tool to improve the epithelial uptake of the loaded protein/peptide. Unfortunately, the stability and the transport mechanisms of the biotherapeutics during the intracellular transportation still remained unclear, leading to the poor transepithelial efficiency. Additionally, developing novel approaches to simultaneously monitor the payload bioactivity during the transport processes is veritably benefit for keeping their bioactivity. In the present study, EGP peptide (KRKKKGKGLGKKRDPCLRKYK), a ligand with high affinity to heparan sulfate proteoglycans (HSPGs), was found remarkably increasing the cellular uptake (4.5-fold) and also surprisingly achieving high transcytosis efficiency (4.2-fold) of poly(lactide-co-glycolide) NPs on Caco-2 cell monolayer. Compared with unmodified NPs (C NPs), EGP modified NPs (EGP NPs) exhibited more desirable colloidal stability within epithelia. In the subsequent study, the...