Multi-functional lipopeptide micelles as a vehicle for curcumin delivery

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 (C 18 H 5 R 7 RGDS, LP) containing H 5 R 7 RGDS heads and stearic acid (C 18 ) 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 5400 times more than that of free CUR. The sequence of H 5 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 H 5 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 (R 8 ), LP micelles can more specifically and efficiently deliver CUR into integrin-overexpressed HepG2 cells than C 18 KR 8 (LP-R 1 ) and C 18 KRGDS (LP-R 2 ) 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.