Cellular uptake mechanism of molecular umbrella.
Molecular umbrella provided a promising avenue for the design of the intracellular delivery of hydrophilic therapeutic agents. However, the limited understanding of its cellular uptake would be a roadblock to its effective application. Herein, we investigate the ability and mechanism of cellular entry of a fluorescently labeled diwalled molecular umbrella, which was synthesized from cholic acid, spermine, and 5-carboxyfluorescein, into Hela cells, with the extent of uptake analyzed by confocal fluorescence microscopy and flow cytometry. It is found that the as-synthesized diwalled molecular umbrella can greatly facilitate cellular uptake of hydrophilic agent, 5-carboxyfluorescein. In vitro experiments with diffuse marker, endocytic marker, and inhibitors suggested that several distinct uptake pathways (e.g., passive diffuse, clathrin-mediated endocytosis, and caveolae/lipid-raft-dependent endocytosis) are involved in the internalization of diwalled molecular umbrella. These results, together with its low toxicity and good biocompatibility, thus demonstrate the suitability of molecular umbrella for application as vectors in drug delivery systems.
Ge
Dongtao
D
Department of Biomaterials/Biomedical Engineering Research Center, College of Materials, State Key Laboratory for Physical Chemistry of Solid Surfaces, and Department of Preclinical Medicine, Medical College, Xiamen University, Xiamen 361005, China.
Wu
Dewang
D
Wang
Zuyong
Z
Shi
Wei
W
Wu
Ting
T
Zhang
Aifeng
A
Hong
Shimin
S
Wang
Jun
J
Zhang
Ye
Y
Ren
Lei
L
D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D001692:Biological Transport; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D002478:Cells, Cultured; D019826:Cholic Acid / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D005452:Fluoresceins / Q000737:chemistry / Q000378:metabolism; D005456:Fluorescent Dyes / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D006367:HeLa Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D008968:Molecular Conformation; D013095:Spermidine / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D013329:Structure-Activity Relationship
D001672:Biocompatible Materials; D004337:Drug Carriers; D005452:Fluoresceins; D005456:Fluorescent Dyes; D008051:Lipid Bilayers; C045132:4-carboxyfluorescein; D019826:Cholic Acid; D013095:Spermidine