TY - JOUR
T1 - Transthyretin as a new transporter of nanoparticles for receptor-mediated transcytosis in rat brain microvessels
AU - Kim, So Yeun
AU - Choi, Eun Sook
AU - Lee, Hyo Jung
AU - Moon, Cheil
AU - Kim, Eunjoo
N1 - Publisher Copyright:
© 2015 Elsevier B.V.
PY - 2015/12/1
Y1 - 2015/12/1
N2 - Many drugs are unable to breach the blood-brain barrier (BBB). Protein-directed transport of nanomedicine by receptor-mediated transcytosis (RMT) has been investigated as a means to overcome this problem. In this study, we screened transporters using an in vitro transcytosis assay system in rat serum to identify candidates that could guide nanoparticles through the BBB by RMT. The proteins that showed over 5-fold decreases in RMT when treated with chloropromazine, an inhibitor of clathrin-dependent endocytosis, were selected and identified by Maldi-TOF mass spectroscopy. Eleven proteins, including transthyretin (Ttr), and creatine kinase-muscle type (CKM), were identified as being capable of penetrating the endothelial cell layer by RMT. Among them, 10 proteins have not yet been used to transport nanomaterials across the BBB. To validate their activity as nanoparticle transporters in vivo, Ttr and CKM were conjugated to the surface of quantum dot (QD) nanoparticles and administrated intravenously. After 8. h, the distribution of Ttr-QDs and CKM-QDs in brain tissue was analyzed. The results showed transcytosis of Ttr-QD conjugates across the BBB in rats as well as in in vitro assays, which was in contrast to the results observed for bare QDs and CKM-QDs. Taken together, these results indicate that Ttr is a new putative transporter for nanomedicines across the BBB.
AB - Many drugs are unable to breach the blood-brain barrier (BBB). Protein-directed transport of nanomedicine by receptor-mediated transcytosis (RMT) has been investigated as a means to overcome this problem. In this study, we screened transporters using an in vitro transcytosis assay system in rat serum to identify candidates that could guide nanoparticles through the BBB by RMT. The proteins that showed over 5-fold decreases in RMT when treated with chloropromazine, an inhibitor of clathrin-dependent endocytosis, were selected and identified by Maldi-TOF mass spectroscopy. Eleven proteins, including transthyretin (Ttr), and creatine kinase-muscle type (CKM), were identified as being capable of penetrating the endothelial cell layer by RMT. Among them, 10 proteins have not yet been used to transport nanomaterials across the BBB. To validate their activity as nanoparticle transporters in vivo, Ttr and CKM were conjugated to the surface of quantum dot (QD) nanoparticles and administrated intravenously. After 8. h, the distribution of Ttr-QDs and CKM-QDs in brain tissue was analyzed. The results showed transcytosis of Ttr-QD conjugates across the BBB in rats as well as in in vitro assays, which was in contrast to the results observed for bare QDs and CKM-QDs. Taken together, these results indicate that Ttr is a new putative transporter for nanomedicines across the BBB.
KW - Blood-brain barrier (BBB)
KW - Drug delivery
KW - Nanomedicine
KW - Receptor-mediated transcytosis
KW - Transthyretin
UR - http://www.scopus.com/inward/record.url?scp=84946573143&partnerID=8YFLogxK
U2 - 10.1016/j.colsurfb.2015.10.050
DO - 10.1016/j.colsurfb.2015.10.050
M3 - Article
C2 - 26562191
AN - SCOPUS:84946573143
SN - 0927-7765
VL - 136
SP - 989
EP - 996
JO - Colloids and Surfaces B: Biointerfaces
JF - Colloids and Surfaces B: Biointerfaces
ER -