Design of cyclic RKKH peptide-conjugated PEG liposomes targeting the integrin 伪₂尾₁ receptor

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• 作者：Nina Ø ; . Knudsen^a ; ^b ; Raymond M. Schiffelers^c ; Lene Jorgensen^a ; Jens Hansen^b ; Sven Frokjaer^a ; Camilla Foged^a ; ^{cfo@farma.ku.dk}
• 关键词：伪2 I-domain ; extracellular insert domain of the integrin 伪2 subunit ; CAMP ; cathelicidin antimicrobial peptide ; DiD ; 1 ; 1&prime ; -dioctadecyl-3 ; 3 ; 3&prime ; 3&prime ; -tetramethylindodicarbocyanine perchlorate ; DMEM ; Dulbecco's modified Eagle's medium ; DSPC ; 1
• 刊名：International Journal of Pharmaceutics
• 出版年：2012
• 期刊代码：24_03785173
• 类别：pha
• 出版时间：30 May, 2012
• 卷：428
• 期：1-2
• 页码：171-177
• 文件大小：573 K

摘要

Peptide conjugation to the surface of stealth liposomes has been studied for liposomal drug targeting to cells expressing specific receptors to provide a site-specific drug delivery. This study investigated the potential of peptide-conjugated liposomes for targeting cells expressing the human integrin 伪₂尾₁ receptor. A 12 amino acid head-to-tail cyclic peptide derived from the Jararhagin protein containing the Arg-Lys-Lys-His (RKKH)-specific binding site was conjugated to the distal ends of poly(ethylene glycol) (PEG) chains on PEGylated liposomes. Epithelial cells expressing the receptor showed increased cellular association and uptake of peptide-conjugated liposomes at 4 掳C, compared to liposomes conjugated with a non-specific peptide. The interaction between cells and peptide-conjugated liposomes was significantly increased at 37 掳C suggesting that a possible uptake mechanism might be energy-dependent endocytosis. In keratinocyte cell cultures, the ligand-conjugated liposomes loaded with the vitamin D₃ analogue calcipotriol induced transcription of the gene encoding the antimicrobial peptide cathelicidin, which is activated through the vitamin D₃ receptor upon binding of vitamin D₃ analogues. This suggests that the liposomes are internalized and that calcipotriol is delivered intracellularly and released in an active form. In conclusion, the 12 amino acid head-to-tail cyclic RKKH peptide seems promising for targeting of liposomes to the integrin 伪₂尾₁ receptor.