期刊
JOURNAL OF CONTROLLED RELEASE
卷 80, 期 1-3, 页码 309-319出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/S0168-3659(02)00017-2
关键词
pH-sensitive liposomes; folate receptor; drug targeting; cytosine-beta-D-arabinofuranoside; gene therapy
资金
- NCI NIH HHS [R01 CA79758-01A1] Funding Source: Medline
pH-sensitive liposomes are designed to promote efficient release of entrapped agents in response to low pH. In this study, novel pH-sensitive liposomes consisting of cationic/anionic lipid combinations are evaluated for intracellular drug and gene delivery. First, liposomes composed of egg phosphatidylcholine. dimethldioctacylammonium bromide (DDAB), cholesteryl hemisuccinate (CHEMS), and Tween-80 (25:25:49:1, mol/mol) were shown to stably entrap calcein at pH 7.4 and undergo rapid content release and irreversible aggregation under acidic pH. Compared to pH-sensitive liposomes incorporating dioleoylphosphatidylethanolamine, these liposomes showed improved retention of pH-sensitivity in the presence of serum. The folate receptor (FR), which is amplified in a wide variety of human tumors, could be targeted by incorporating 0.1 mol% folate-polyethyleneglycol-phosphatidylethanolamine (f-PEG-PE) into liposomes. f-PEG-PE has been shown to facilitate FR-mediated endocytosis of liposomes into KB human oral cancer cells, which express amplified FR. FR-targeted pH-sensitive liposomes produced increased cytosolic release of entrapped calcein. as shown by fluorescence microscopy, and enhanced cytotoxicity of entrapped cytosine-beta-D-arabinofuranoside. as shown by an 11-fold reduction in the IC50 in KB cells. compared to FR-targeted non-pH-sensitive liposomes. Furthermore, FR-targeted pH-sensitive liposomes composed of DDAB/CHEMS/f-PEG-PE. combined with polylysine-condensed plasmid DNA, were shown to mediate FR-specific delivery of a luciferase reporter gene into KB cells in the presence of 10% serum. These findings suggest that cationic lipid-containing pH-sensitive liposomes, combined with FR targeting, are effective vehicles for intracellular drug and gene delivery. (C) 2002 Elsevier Science B.V. All rights reserved.
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