排序方式: 共有1条查询结果,搜索用时 15 毫秒
1
1.
Enhanced heparan sulfate proteoglycan-mediated uptake of cell-penetrating peptide-modified liposomes
Marty C Meylan C Schott H Ballmer-Hofer K Schwendener RA 《Cellular and molecular life sciences : CMLS》2004,61(14):1785-1794
Protein transduction domains (PTDs) are used to enhance cellular uptake of drugs, proteins, polynucleotides
or liposomes. In this study, functionalized Antennapedia (Antp, aa 43–-58) and HIV Tat (aa 47–57)
peptides were coupled to small unilamellar liposomes via thiol-maleimide linkage. Modified liposomes showed higher
uptake into a panel of cell lines including tumor and dendritic cells than unmodified control liposomes. Liposome
uptake was time and concentration dependent as analyzed by flow cytometry and live-cell microscopy. At least 100
PTD molecules per small unilamellar liposome (100 ± 30 nm) were necessary for efficient translocation into
cells. Cellular uptake of PTD-modified liposomes was 15- to 25-fold increased compared to unmodified liposomes and
was inhibited by preincubation of liposomes with heparin. Glycosaminoglycan-deficient CHO cells showed dramatically
reduced cell association of PTD-modified liposomes, confirming the important role of heparan sulfate proteoglycans
in PTD-mediated uptake. Antp-liposomes used as carriers of the cytotoxic drug
N4-octadecyl-1--D-arabinofuranosylcytosine-(5- 5)-3-C-ethinylcytidine
showed a reduction of the IC50 by 70% on B16F1 melanoma cells compared with unmodified
liposomes. PTD-functionalized liposomes, particularly Antp-liposomes, represent an interesting novel carrier
system for enhanced cell-specific delivery of a large variety of liposome-entrapped molecules.Received 16 April 2004; received after revision 13 May 2004; accepted 25 May 2004 相似文献
1