Transcytosis: an effective mechanism to enhance nanoparticle extravasation and infiltration through biological barriers

Abstract Nanoparticles (NPs) 1 have been explored as drugs carriers for treating tumors and central nervous system (CNS) 2 diseases and for oral administration. However, they lack satisfactory clinical efficacy due to poor extravasation and infiltration through biological barriers to target tissues. Most clinical antitumor NPs have been designed based on enhanced permeability and retention effects which are insufficient and heterogeneous in human tumors. The tight junctions 3 3 TJs: tight junctions of the blood–brain barrier 4 4 BBB: blood–brain barrier and the small intestinal epithelium severely impede NPs from being transported into the CNS and blood circulation, respectively. By contrast, transcytosis enables NPs to bypass these physiological barriers and enhances their infiltration into target tissues by active transport. Here, we systematically review the mechanisms and putative application of NP transcytosis for targeting tumor and CNS tissues, explore oral NP administration, and propose future research directions in the field of NP transcytosis.