Liprotides: Nano-Sized Cytotoxic Protein-Fatty Acid Complexes with a Core-Shell or Multi-Layer Structure

Abstract

A cytotoxic protein-fatty acid complex known as HAMLET is a complex which can target cancer cells. The complex discovered in 1995 is composed of the milk protein alpha-lactalbumin (aLA) and the cis-monounsaturated fatty acid, oleic acid (OA) [1]. We have completed a Small Angle X-ray Scattering study that implied a core-shell structure of this complex: the core consists of fatty acid in a micelle-like form, while the protein surrounds the micellar core [2].This core-shell structure is also observed for unrelated proteins e.g. equine lysozyme, bovine serum albumin and S6 ribosomal protein in complex with OA [2,3]. Likewise is the core-shell structure observed for complexes composed of aLA and other fatty-acids provided they contain cis (but not trans) double bonds.A related but larger structure can be obtained by having a higher molar ratio of fatty acids to protein under complex preparation (pH 7.4 and 25-80oC). This larger structure is called multi-layer because they have an additional layer of both fatty acid and protein surrounding the outside of the core-shell structure. We have introduced the term “liprotides” for complexes obtaining the core-shell or multi-layer structure.The protein component of liprotides solubilizes the hydrophobic fatty acid component and binds to them strongly but reversibly. This allows transfer of the cytotoxic fatty acids to other hydrophobic phases e.g. cells. The transfer of fatty acids to cells entails cell death and release of the protein component. All this make liprotides highly attractive and versatile nano-tool with broad potential for using liprotides for encapsulation and delivery of small hydrophobic materials for use in pharmaceuticals, food technology, cosmetics and other personal-care products [4].[1] 1995, PNAS 92, 8064-8068.[2] 2014, Chembiochem 15, 2693-2702.[3] 2010, Journal of MB 398, 351-361.[4] 2015, Biochemistry 54, 4815-4823.