Multi-functional lipopeptide micelles as a vehicle for curcumin delivery

Abstract Curcumin (CUR) is a kind of natural polyphenol with low aqueous solubility, poor bioavailability and favorable antitumor activity. In order to enhance anti-tumor activity and efficient delivery of CUR, an amphiphilic lipopeptide (C18H5R7RGDS, LP) containing H5R7RGDS heads and stearic acid (C18) tails was prepared by solid-phase peptide synthesis. Spherical LP micelles of ∼50 nm were self-assembled in PBS (pH 7.0) with good dispersion and significantly improved the aqueous solubility of CUR by 5,400 times more than that of free CUR. The sequence of H5 in LP endowed the CUR-loaded LP micelles with good pH-responsive drug release behavior. In the case of pH 5.0, the electrostatic repulsion interaction among the ionized H5 fraction destroyed the structure of micelles, leading to significantly accelerated CUR release behavior. Hemolysis assay and proliferation inhibition test of normal cells confirmed apparently the excellent biocompatibility of LP. CUR-loaded LP micelles showed much higher cell growth inhibition on HepG2 cells and lower cytotoxicity on L02 cells than free CUR. With integrin-targeting sequence (RGD) and cell penetrating peptide (R8), LP micelles can more specifically and efficiently deliver CUR into integrin-overexpressed HepG2 cells than C18KR8 (LP-R1) and C18KRGDS (LP-R2) micelles. Combined with the enhanced drug solubility, distinctive pH-sensitive property and good tumor targeting, such LP micelles may have the clinical potential for tumor-targeting delivery.