Escape sites from the endo-lysosomal trafficking route manipulate exocytosis of nanoparticles in polar epithelium

Abstract

The endo–lysosomal pathway is a major barrier for the trans-epithelial transport of nanoparticles (NPs), but escape strategies could facilitate trans-epithelial delivery. Based on the polarization properties of the epithelium, different escape compartments may result in different exocytosis fates of NPs and further affect the delivery efficiency. Therefore, optimizing the escape sites is critical for trans-epithelial delivery. Here, commonly used PEG-coated-poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles were fabricated as model nanoparticles (MNPs) and the intestinal epithelium was chosen as the polarized epithelium. The MNPs were incubated with different endosomolytic agents for early endosomal escape, late endosomal escape and lysosomal escape, respectively. According to in vitro and in vivo studies, MNPs escaping from early endosomes and late endosomes exhibited stronger capacity for trans-epithelial transport than those escaping from lysosomes. By further probing into the mechanism, we surprisingly found that although MNPs escaping from early endosomes quickly egressed from the apical side of epithelia, they were subsequently followed by “reuptake” via caveolae and trafficked through the endoplasmic reticulum–Golgi apparatus (ER/GA) secretory pathway, achieving efficient trans-epithelial transport; MNPs escaping from late endosomes, which were located near the nucleus, were prone to enter the ER/GA for efficient basolateral exocytosis. However, MNPs escaping from lysosomes were detained within cells by autophagosomes. Collectively, our research suggested that early endosomes and late endosomes were ideal escape sites for trans-epithelial delivery.

Graphical abstract: Escape sites from the endo-lysosomal trafficking route manipulate exocytosis of nanoparticles in polar epithelium

Supplementary files

Article information

Article type
Paper
Submitted
01 Feb 2024
Accepted
26 Mar 2024
First published
02 Apr 2024

Biomater. Sci., 2024, Advance Article

Escape sites from the endo-lysosomal trafficking route manipulate exocytosis of nanoparticles in polar epithelium

L. Wang, Y. Li, X. Liu, L. Xing, R. Wu and Y. Huang, Biomater. Sci., 2024, Advance Article , DOI: 10.1039/D4BM00174E

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements