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Peptide Anchor for Folate-Targeted Liposomal Delivery
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2015 (English)In: Biomacromolecules, ISSN 1525-7797, E-ISSN 1526-4602, Vol. 16, no 9, 2904-2910 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2015. Vol. 16, no 9, 2904-2910 p.
Keyword [en]
Surfactant Protein-D, Cyclooxygenase-2 Inhibitor, Inflammatory Response, Carbon-Monoxide, In-Vitro, Celecoxib, Cancer, Cells, Methotrexate, Mechanisms
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) Biochemistry and Molecular Biology Cell Biology
Identifiers
URN: urn:nbn:se:kth:diva-174926DOI: 10.1021/acs.biomac.5b00823ISI: 000361341700037PubMedID: 26241560Scopus ID: 2-s2.0-84941584525OAI: oai:DiVA.org:kth-174926DiVA: diva2:865268
Note

QC 20151027

Available from: 2015-10-27 Created: 2015-10-09 Last updated: 2017-12-01Bibliographically approved

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Härmark, JohanMoreira, Alexandra

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