Use of Dual-Ligand Modification in Kupffer Cell-Targeted Liposomes To Examine the Contribution of Kupffer Cells to Accelerated Blood Clearance Phenomenon.
Mol Pharm
; 15(7): 2548-2558, 2018 07 02.
Article
em En
| MEDLINE
| ID: mdl-29768009
The "accelerated blood clearance (ABC) phenomenon" is known to be involved in the adaptive immune system. Regretfully, the relationship between the ABC phenomenon and innate immune system, especially with respect to Kupffer cells (KCs) has been largely unexplored. In this study, the contribution of KCs to ABC was examined using the 4-aminophenyl-α-d-mannopyranoside (APM) lipid derivative DSPE-PEG2000-APM (DPM) and the 4-aminophenyl-ß-l-fucopyranoside (APF) lipid derivative DSPE-PEG2000-APF (DPF) as ligands for mannose/fucose receptors on KCs, which were synthesized and modified on the surface of liposomes. The results of cellular liposome uptake in vitro and biodistribution in vivo indicated that DPM and DPF comodified liposomes (MFPL5-5) present the strongest capability of KC-targeting among all preparations tested. In rats pretreated with MFPL5-5 instead of PEGylated liposomes (PL), the ABC phenomenon was significantly enhanced and the distribution of liposomes in the liver was increased. Cellular uptake of the second injection of PL in vivo demonstrated that KCs was responsible for the uptake. Furthermore, compared to pretreatment with PL, the uptake of second injection of PL was more enhanced when pretreated with MFPL5-5. These findings suggest that KCs, which are considered traditional members of the innate immune system, play a crucial role in the ABC phenomenon and act as a supplement to the phenomenon.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores de Superfície Celular
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Lectinas Tipo C
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Lectinas de Ligação a Manose
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Imunidade Adaptativa
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Células de Kupffer
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Fígado
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Mol Pharm
Ano de publicação:
2018
Tipo de documento:
Article