Efficient intracellular drug and gene delivery using folate receptor-targeted pH-sensitive liposomes composed of cationic/anionic lipid combinations

Guangfeng Shi, Wenjin Guo, Stacy Stephenson, Robert J. Lee

Research output: Contribution to journalArticle

157 Citations (Scopus)

Abstract

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, dimethyldioctadecylammonium 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-β-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.

Original languageEnglish (US)
Pages (from-to)309-319
Number of pages11
JournalJournal of Controlled Release
Volume80
Issue number1-3
DOIs
StatePublished - Apr 23 2002

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Folic Acid
Liposomes
Lipids
Pharmaceutical Preparations
Genes
KB Cells
Polylysine
Polysorbates
Mouth Neoplasms
Cytosine
Endocytosis
Luciferases
Serum
Phosphatidylcholines
Reporter Genes
Fluorescence Microscopy
Inhibitory Concentration 50
Ovum
Plasmids
DNA

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

Cite this

Efficient intracellular drug and gene delivery using folate receptor-targeted pH-sensitive liposomes composed of cationic/anionic lipid combinations. / Shi, Guangfeng; Guo, Wenjin; Stephenson, Stacy; Lee, Robert J.

In: Journal of Controlled Release, Vol. 80, No. 1-3, 23.04.2002, p. 309-319.

Research output: Contribution to journalArticle

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