Peptide Anchor for Folate-Targeted Liposomal Delivery

Specific folate receptors are abundantly overexpressed in chronically activated macrophages and in most cancer cells. Directed folate receptor targeting using liposomes is usually achieved using folate linked to a phospholipid or cholesterol anchor. This link is formed using a large spacer like poly...

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Bibliographic Details
Published in:Biomacromolecules 2015-09, Vol.16 (9), p.2904-2910
Main Authors: Nogueira, Eugénia, Mangialavori, Irene C, Loureiro, Ana, Azoia, Nuno G, Sárria, Marisa P, Nogueira, Patrícia, Freitas, Jaime, Härmark, Johan, Shimanovich, Ulyana, Rollett, Alexandra, Lacroix, Ghislaine, Bernardes, Gonçalo J. L, Guebitz, Georg, Hebert, Hans, Moreira, Alexandra, Carmo, Alexandre M, Rossi, Juan Pablo F. C, Gomes, Andreia C, Preto, Ana, Cavaco-Paulo, Artur
Format: Article
Language:English
Subjects:
Caco-2 Cells
Cancer
Carbon-Monoxide
Celecoxib
Cells
Cholesterol - chemistry
Cholesterol - pharmacology
Cyclooxygenase-2 Inhibitor
Drug Delivery Systems - methods
Folic Acid - chemistry
Folic Acid - pharmacology
Humans
In-Vitro
Inflammatory Response
Life Sciences
Lipid Bilayers - chemistry
Lipid Bilayers - pharmacology
Liposomes
Mechanisms
Medicin och hälsovetenskap
Methotrexate
Peptides - chemistry
Peptides - pharmacology
Phospholipids - chemistry
Phospholipids - pharmacology
Science & Technology
Surfactant Protein-D
Toxicology
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Summary:Specific folate receptors are abundantly overexpressed in chronically activated macrophages and in most cancer cells. Directed folate receptor targeting using liposomes is usually achieved using folate linked to a phospholipid or cholesterol anchor. This link is formed using a large spacer like polyethylene glycol. Here, we report an innovative strategy for targeted liposome delivery that uses a hydrophobic fragment of surfactant protein D linked to folate. Our proposed spacer is a small 4 amino acid residue linker. The peptide conjugate inserts deeply into the lipid bilayer without affecting liposomal integrity, with high stability and specificity. To compare the drug delivery potential of both liposomal targeting systems, we encapsulated the nuclear dye Hoechst 34580. The eventual increase in blue fluorescence would only be detectable upon liposome disruption, leading to specific binding of this dye to DNA. Our delivery system was proven to be more efficient (2-fold) in Caco-2 cells than classic systems where the folate moiety is linked to liposomes by polyethylene glycol.
ISSN:1525-7797
1526-4602
1526-4602
DOI:10.1021/acs.biomac.5b00823