Biophysical mechanisms of phospholipase A2 activation and their use in liposome-based drug delivery

Kent Jorgensen, Jesper Davidsen, Ole G. Mouritsen*

*Corresponding author for this work

    Research output: Contribution to journalJournal articleResearchpeer-review

    106 Citations (Scopus)

    Abstract

    Secretory phospholipase A2 (PLA2) is a ubiquitous water-soluble enzyme found in venom, pancreatic, and cancerous fluid. It is also known to play a role in membrane remodeling processes as well as in cellular signaling cascades. PLA2 is interfacially active and functions mainly on organized types of substrate, e.g. micelles and lipid bilayers. Hence the activity of the enzyme is modulated by the lateral organization and the physical properties of the substrate, in particular the structure in the nanometer range. The evidence for nano-scale structure and lipid domains in bilayers is briefly reviewed. Results obtained from a variety of experimental and theoretical studies of PLA2 activity on lipid-bilayer substrates are then presented which provide insight into the biophysical mechanisms of PLA2 activation on lipid bilayers and liposomes of different composition. The insight into these mechanisms has been used to propose a novel principle for liposomal drug targeting, release, and absorption triggered by secretory PLA2.

    Original languageEnglish
    JournalFEBS Letters
    Volume531
    Issue number1
    Pages (from-to)23-27
    Number of pages5
    ISSN0014-5793
    DOIs
    Publication statusPublished - 30 Oct 2002

    Keywords

    • Anti-cancer drug
    • Lipid domain
    • Phospholipase A2
    • Pro-drug
    • Pro-enhancer
    • Stealth liposome

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