Abstract | BACKGROUND: A novel dual ligand-modified liposome, folic acid-tethered Pep-1 peptide-conjugated liposomal nanocarrier (FP-Lipo), was designed to overcome the nonselectivity of conventional penetrating peptide-tagged nanoparticulates and to provide the advantage of selective targeting of the folic acid receptor, which is frequently overexpressed on epithelial cancer cells. METHODS: FP-Lipo was prepared by a sequential process of formation of a maleimide-derivatized small unilamellar vesicle, postinsertion of distearoyl phosphatidyl ethanolamine- polyethylene glycol 2000-folate to the vesicle, and Pep-1 peptide conjugation via thiol-maleimide linkage. Conformational and physical characteristics of the FP-Lipo nanocarriers were investigated for the extent of Pep-1 peptide and folic acid on the surface, vesicle size, and zeta potential. In vitro cellular uptake behaviors of the novel carrier containing a fluorescein dextran isothiocyanate probe were examined by spectrophotometry or by confocal laser scanning microscopy. RESULTS: A novel nanocarrier bearing approximately 750 folate ligands and 100 penetrating peptides per vesicle was successfully prepared. The physical properties were as follows: 140 nm in size; 5 mV in zeta potential; less than 0.3 in polydispersity index. An in vitro cellular uptake study revealed that the FP-Lipo nanocarrier system exhibited more than twofold enhanced translocation into the folic acid receptor-positive HeLa cells compared with the single Pep-1 peptide-modified liposome. Meanwhile, its cellular association and internalization into the folic acid receptor-negative normal HaCaT cells was comparable with that of Pep-1 peptide-modified liposome. CONCLUSION:
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Authors | Myung Joo Kang, Sang Han Park, Mean Hyung Kang, Min Jung Park, Young Wook Choi |
Journal | International journal of nanomedicine
(Int J Nanomedicine)
Vol. 8
Pg. 1155-65
( 2013)
ISSN: 1178-2013 [Electronic] New Zealand |
PMID | 23515421
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Liposomes
- Pep-1 peptide
- Peptides
- Cysteamine
- Folic Acid
- Fluorescein-5-isothiocyanate
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Topics |
- Amino Acid Sequence
- Cell Line, Transformed
- Cell Survival
(drug effects)
- Cysteamine
(administration & dosage, analogs & derivatives, chemistry, pharmacokinetics)
- Drug Delivery Systems
(methods)
- Fluorescein-5-isothiocyanate
- Folic Acid
(administration & dosage, chemistry, pharmacokinetics)
- HeLa Cells
- Humans
- Intracellular Space
(chemistry, metabolism)
- Keratinocytes
(cytology, drug effects, metabolism)
- Liposomes
(administration & dosage, chemistry, pharmacokinetics)
- Microscopy, Fluorescence
- Molecular Sequence Data
- Nanoparticles
(administration & dosage, chemistry)
- Peptides
(administration & dosage, chemistry, pharmacokinetics)
- Protein Conformation
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