TY - JOUR
T1 - Functionalization of liposomes with ApoE-derived peptides at different density affects cellular uptake and drug transport across a blood-brain barrier model
AU - Re, Francesca
AU - Cambianica, Ilaria
AU - Zona, Cristiano
AU - Sesana, Silvia
AU - Gregori, Maria
AU - Rigolio, Roberta
AU - La Ferla, Barbara
AU - Nicotra, Francesco
AU - Forloni, Gianluigi
AU - Cagnotto, Alfredo
AU - Salmona, Mario
AU - Masserini, Massimo
AU - Sancini, Giulio
PY - 2011/10
Y1 - 2011/10
N2 - A promising strategy to enhance blood-brain barrier penetration by drugs is the functionalization of nanocarriers with uptake-facilitating ligands. We studied the cellular uptake, by cultured RBE4 brain capillary endothelial cells, of nanoliposomes (NLs) covalently coupled with monomer or tandem dimer of apolipoprotein E (ApoE)-derived peptides (residues 141-150), at various densities. NLs without functionalization did not show either relevant membrane accumulation or cellular uptake, as monitored by confocal microscopy and quantified by fluorescence-activated cell sorting. Functionalization with peptides mediated an efficient NLs uptake that increased with peptide density; NLs carrying monomeric peptide performed the best. Moreover, we studied the ability of ApoE-NLs to enhance the transport of a drug payload through a RBE4 cell monolayer. The permeability of a tritiated curcumin derivative was enhanced after its entrapment into ApoE-NLs, in particular those functionalized with the dimer (+83% with respect to free drug, P <0.01). Thus, these NLs appear particularly suitable for implementing further strategies for drug brain targeting. From the Clinical Editor: Re and her collaborators present a method for delivering nanoliposomes via the blood brain barrier by utilizing peptide fragments including monomers or tandem dimers ApoE. This method may enable enhanced nanoliposome associated drug delivery via the blood-brain barrier, which would have enormous significance in neurodegenerative and other CNS disorders.
AB - A promising strategy to enhance blood-brain barrier penetration by drugs is the functionalization of nanocarriers with uptake-facilitating ligands. We studied the cellular uptake, by cultured RBE4 brain capillary endothelial cells, of nanoliposomes (NLs) covalently coupled with monomer or tandem dimer of apolipoprotein E (ApoE)-derived peptides (residues 141-150), at various densities. NLs without functionalization did not show either relevant membrane accumulation or cellular uptake, as monitored by confocal microscopy and quantified by fluorescence-activated cell sorting. Functionalization with peptides mediated an efficient NLs uptake that increased with peptide density; NLs carrying monomeric peptide performed the best. Moreover, we studied the ability of ApoE-NLs to enhance the transport of a drug payload through a RBE4 cell monolayer. The permeability of a tritiated curcumin derivative was enhanced after its entrapment into ApoE-NLs, in particular those functionalized with the dimer (+83% with respect to free drug, P <0.01). Thus, these NLs appear particularly suitable for implementing further strategies for drug brain targeting. From the Clinical Editor: Re and her collaborators present a method for delivering nanoliposomes via the blood brain barrier by utilizing peptide fragments including monomers or tandem dimers ApoE. This method may enable enhanced nanoliposome associated drug delivery via the blood-brain barrier, which would have enormous significance in neurodegenerative and other CNS disorders.
KW - ApoE peptide
KW - Blood-brain barrier
KW - Brain endothelial cells
KW - Nanoliposomes
UR - http://www.scopus.com/inward/record.url?scp=80053209371&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=80053209371&partnerID=8YFLogxK
U2 - 10.1016/j.nano.2011.05.004
DO - 10.1016/j.nano.2011.05.004
M3 - Article
C2 - 21658472
AN - SCOPUS:80053209371
VL - 7
SP - 551
EP - 559
JO - Nanomedicine: Nanotechnology, Biology, and Medicine
JF - Nanomedicine: Nanotechnology, Biology, and Medicine
SN - 1549-9634
IS - 5
ER -