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 5400 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.

姜黄素（CUR）是一种水溶性低，生物利用度差，抗肿瘤活性好的天然多酚。为了增强CUR的抗肿瘤活性和有效递送，通过固相肽制备了含有H ₅ R ₇ RGDS头和硬脂酸（C ₁₈）尾的两亲性脂肽（C ₁₈ H ₅ R ₇ RGDS，LP）。合成。约50 nm的球形LP胶束在具有良好分散性的PBS（pH 7.0）中自组装，与游离CUR相比，其CUR的水溶性大大提高了5400倍。H ₅的序列在LP中，CUR负载的LP胶束具有良好的pH响应药物释放行为。在pH 5.0的情况下，电离的H ₅馏分之间的静电排斥相互作用破坏了胶束的结构，从而导致CUR释放行为明显加速。正常细胞的溶血分析和增殖抑制试验显然证实了LP的优异生物相容性。与游离CUR相比，负载CUR的LP胶束对HepG2细胞具有更高的细胞生长抑制作用，对L02细胞具有更低的细胞毒性。与C ₁₈ KR ₈（LP-R ₁）相比，有了整联蛋白靶向序列（RGD）和细胞穿透肽（R ₈），LP胶束可以更特异性和有效地将CUR递送至过表达整联蛋白的HepG2细胞中。）和C ₁₈ KRGDS（LP-R ₂）胶束。结合提高的药物溶解度，独特的pH敏感特性和良好的肿瘤靶向性，此类LP胶束可能具有靶向肿瘤的临床潜力。