title: The effect of hydrophilic and hydrophobic structure of amphiphilic polymeric micelles on their transport in epithelial MDCK cells.
abstract: The interaction of nanocarriers with cells including their transcellular behavior is vital not only for a drug delivery system, but also for the safety of nanomaterials. In an attempt to clarify how the structures of polymers impact the transport mechanisms of their nanocarriers in epithelial cells, three amphiphilic polymers (PEEP-PCL, PEG-PCL and PEG-DSPE) with different hydrophilic or hydrophobic blocks were synthesized or chosen to form different micelle systems here. The endocytosis, exocytosis, intracellular colocalization, paracellular permeability and transcytosis of these micelle systems were compared using Förster resonance energy transfer analysis, real-time confocal images, colocalization assay, transepithelial electrical resistance study, and so on. All micelle systems were found intact during the studies with cells. The endocytosis and exocytosis studies with undifferentiated MDCK cells and the transcytosis study with differentiated MDCK monolayers all indicated the fact that PEG-DSPE micelles achieved the most and fastest transport, followed by PEG-PCL and PEEP-PCL in order. These might be because DSPE has higher hydrophobicity than PCL while PEG has lower hydrophilicity than PEEP. Different in hydrophilic or hydrophobic structures, all kinds of micelles demonstrated similar pathways during endocytosis and exocytosis, both caveolae- and clathrin-mediated but with difference in degree. The colocalization studies revealed different behaviors in intracellular trafficking among the three polymer micelles, suggesting the decisive role of hydrophilic shells on this process. Finally, all micelle systems did not impact the paracellular permeability of test cell monolayer. In conclusion, the hydrophilic and hydrophobic structures of test micelles could influence their transport ability, intracellular trafficking and the transport level under each pathway in MDCK cells.
authors.affiliation: The State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Yu
authors.forename: Bing
authors.initials: B
authors.lastname: He
authors.forename: Meng-Hua
authors.initials: MH
authors.lastname: Xiong
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.forename: Lan
authors.initials: L
authors.lastname: Yuan
authors.forename: Ling
authors.initials: L
authors.lastname: Ma
authors.forename: Wen-Bing
authors.initials: WB
authors.lastname: Dai
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Xing-Lin
authors.initials: XL
authors.lastname: Wang
authors.forename: Xue-Qing
authors.initials: XQ
authors.lastname: Wang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000818:Animals; D004285:Dogs; D004705:Endocytosis; D005089:Exocytosis; D057927:Hydrophobic and Hydrophilic Interactions; D007783:Lactones / Q000032:analysis / Q000378:metabolism*; D061985:Madin Darby Canine Kidney Cells / Q000166:cytology* / Q000378:metabolism; D008823:Micelles; D010539:Permeability; D010714:Phosphatidylethanolamines / Q000032:analysis / Q000378:metabolism*; D011091:Polyesters / Q000032:analysis / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000032:analysis / Q000378:metabolism*; D013501:Surface-Active Agents / Q000032:analysis / Q000378:metabolism
chemical_list: D007783:Lactones; D008823:Micelles; D010714:Phosphatidylethanolamines; D011091:Polyesters; D013501:Surface-Active Agents; C557288:poly(epsilon-caprolactone)-block-poly(ethyl ethylene phosphate); C521904:poly(ethylene glycol)-block-poly(epsilon-caprolactone); C107570:polyethylene glycol-distearoylphosphatidylethanolamine; D011092:Polyethylene Glycols