TY - JOUR
T1 - Internalization and transport of PEGylated lipid-based mixed micelles across Caco-2 cells mediated by scavenger receptor B1
AU - Su, Xiangjie
AU - Ramírez-Escudero, Mercedes
AU - Sun, Feilong
AU - van den Dikkenberg, Joep B.
AU - van Steenbergen, Mies J.
AU - Pieters, Roland J.
AU - Janssen, Bert J.C.
AU - van Hasselt, Peter M.
AU - Hennink, Wim E.
AU - van Nostrum, Cornelus F.
N1 - Funding Information:
Funding: X. Su is supported by a PhD scholarship from China Scholarship Council (CSC) (File no. 201707040097).
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/12
Y1 - 2021/12
N2 - The aim of this study was to get insight into the internalization and transport of PEGylat-ed mixed micelles loaded by vitamin K, as mediated by Scavenger Receptor B1 (SR-B1) that is abun-dantly expressed by intestinal epithelium cells as well as by differentiated Caco-2 cells. Inhibition of SR-B1 reduced endocytosis and transport of vitamin-K-loaded 0%, 30% and 50% PEGylated mixed micelles and decreased colocalization of the micelles with SR-B1. Confocal fluorescence mi-croscopy, fluorescence-activated cell sorting (FACS) analysis, and surface plasmon resonance (SPR) were used to study the interaction between the mixed micelles of different compositions (varying vitamin K loading and PEG content) and SR-B1. Interaction of PEGylated micelles was independent of the vitamin K content, indicating that the PEG shell prevented vitamin K exposure at the surface of the micelles and binding with the receptor and that the PEG took over the micelles’ ability to bind to the receptor. Molecular docking calculations corroborated the dual binding of both vita-min K and PEG with the binding domain of SR-B1. In conclusion, the improved colloidal stability of PEGylated mixed micelles did not compromise their cellular uptake and transport due to the affin-ity of PEG for SR-B1. SR-B1 is able to interact with PEGylated nanoparticles and mediates their subsequent internalization and transport.
AB - The aim of this study was to get insight into the internalization and transport of PEGylat-ed mixed micelles loaded by vitamin K, as mediated by Scavenger Receptor B1 (SR-B1) that is abun-dantly expressed by intestinal epithelium cells as well as by differentiated Caco-2 cells. Inhibition of SR-B1 reduced endocytosis and transport of vitamin-K-loaded 0%, 30% and 50% PEGylated mixed micelles and decreased colocalization of the micelles with SR-B1. Confocal fluorescence mi-croscopy, fluorescence-activated cell sorting (FACS) analysis, and surface plasmon resonance (SPR) were used to study the interaction between the mixed micelles of different compositions (varying vitamin K loading and PEG content) and SR-B1. Interaction of PEGylated micelles was independent of the vitamin K content, indicating that the PEG shell prevented vitamin K exposure at the surface of the micelles and binding with the receptor and that the PEG took over the micelles’ ability to bind to the receptor. Molecular docking calculations corroborated the dual binding of both vita-min K and PEG with the binding domain of SR-B1. In conclusion, the improved colloidal stability of PEGylated mixed micelles did not compromise their cellular uptake and transport due to the affin-ity of PEG for SR-B1. SR-B1 is able to interact with PEGylated nanoparticles and mediates their subsequent internalization and transport.
KW - Epithelial transport
KW - Mixed micelles
KW - PEGylation
KW - Scavenger receptor B1
KW - Vitamin K
UR - http://www.scopus.com/inward/record.url?scp=85120174052&partnerID=8YFLogxK
U2 - 10.3390/pharmaceutics13122022
DO - 10.3390/pharmaceutics13122022
M3 - Article
AN - SCOPUS:85120174052
SN - 1999-4923
VL - 13
JO - Pharmaceutics
JF - Pharmaceutics
IS - 12
M1 - 2022
ER -