The effect of cholesterol in a liposomal Muc1 vaccine
| Autor: | Michael M Batenjany, Mircea C. Popescu, Shalini Bansal, Yuqing Guo, Mary E. Neville, Richard J. Robb, Lawrence T. Boni |
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| Rok vydání: | 2001 |
| Předmět: |
Mucin-based lipopeptide
1 2-Dipalmitoylphosphatidylcholine Molecular Sequence Data Biophysics Fluorescence Polarization In Vitro Techniques Cancer Vaccines Biochemistry Lipid A Interferon-gamma Mice chemistry.chemical_compound Mole Animals Amino Acid Sequence Lymphocytes MUC1 Drug Carriers Liposome Calorimetry Differential Scanning Cholesterol Bilayer Mucin-1 Vaccination Lipopeptide Cell Biology Peptide Fragments chemistry Liposomes Anisotropy lipids (amino acids peptides and proteins) Lymph Nodes Vaccine Spleen Fluorescence anisotropy |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Biomembranes. 1514:280-290 |
| ISSN: | 0005-2736 |
| DOI: | 10.1016/s0005-2736(01)00383-2 |
| Popis: | A liposomal Muc1 mucin vaccine for treatment of adenocarcinomas was formulated by incorporating a synthetic Muc1 mucin-based lipopeptide and Lipid A into a DPPC/cholesterol bilayer. Vaccination of mice with the liposomal formulation produced a peptide-specific immune response dependent on the cholesterol content. The response occurred at a threshold of 20–23 mol% cholesterol, and was optimal at cholesterol levels of ≥30 mol%. To understand this cholesterol dependency, we studied the effect of cholesterol on the liposomal bilayer and surface properties. Freeze-fracture electron microscopy showed a unique surface texture that was codependent upon cholesterol (≥20 mol%) and lipopeptide content. Fluorescence anisotropy measurements exhibited a significant decrease in the rotational motion of 1,6-diphenyl-1,3,5-hexatriene in formulations containing >20 mol% cholesterol and only in the presence of the lipopeptide. At 20 mol% cholesterol and with lipopeptide, DSC showed a significant increase in the main phase transition of the DPPC bilayers, while Raman spectroscopy indicated a more ordered arrangement of DPPC molecules compared to control liposomes containing DPPC/cholesterol alone. Taken together, the data suggest the presence of lipopeptide-rich microdomains at and above a threshold of 20 mol% cholesterol that may play a role in the induction of a peptide-specific immunological response. |
| Databáze: | OpenAIRE |
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