Tianjin Key Laboratory of Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science and Peking Union Medical College, People's Republic of China.
Int J Nanomedicine. 2014;9:197-207. doi: 10.2147/IJN.S55875. Epub 2013 Dec 24.
The poor aqueous solubility and low bioavailability of curcumin restrict its clinical application for cancer treatment. In this study, a novel tumor-targeting nanofiber carrier was developed to improve the solubility and tumor-targeting ability of curcumin using a self-assembled Nap-GFFYG-RGD peptide. The morphologies of the peptide nanofiber and the curcumin-encapsulated nanofiber were visualized by transmission electron microscopy. The tumor-targeting activity of the curcumin-encapsulated Nap-GFFYG-RGD peptide nanofiber (f-RGD-Cur) was studied in vitro and in vivo, using Nap-GFFYG-RGE peptide nanofiber (f-RGE-Cur) as the control. Curcumin was encapsulated into the peptide nanofiber, which had a diameter of approximately 10-20 nm. Curcumin showed sustained-release behavior from the nanofibers in vitro. f-RGD-Cur showed much higher cellular uptake in αvβ3 integrin-positive HepG2 liver carcinoma cells than did non-targeted f-RGE-Cur, thereby leading to significantly higher cytotoxicity. Ex vivo studies further demonstrated that curcumin could accumulate markedly in mouse tumors after administration of f-RGD-Cur via the tail vein. These results indicate that Nap-GFFYG-RGD peptide self-assembled nanofibers are a promising hydrophobic drug delivery system for targeted treatment of cancer.
姜黄素的水溶性差和生物利用度低限制了其在癌症治疗中的临床应用。本研究采用自组装的 Nap-GFFYG-RGD 肽开发了一种新型肿瘤靶向纳米纤维载体，以提高姜黄素的溶解度和肿瘤靶向能力。通过透射电子显微镜观察了肽纳米纤维和载姜黄素纳米纤维的形态。使用 Nap-GFFYG-RGE 肽纳米纤维（f-RGE-Cur）作为对照，研究了载姜黄素的 Nap-GFFYG-RGD 肽纳米纤维（f-RGD-Cur）在体外和体内的肿瘤靶向活性。姜黄素被包裹在纳米纤维中，其直径约为 10-20nm。姜黄素在体外从纳米纤维中表现出持续释放行为。f-RGD-Cur 在 αvβ3 整联蛋白阳性 HepG2 肝癌细胞中的细胞摄取率明显高于非靶向 f-RGE-Cur，从而导致细胞毒性显著增加。离体研究进一步表明，尾静脉给予 f-RGD-Cur 后，姜黄素可在小鼠肿瘤中明显积聚。这些结果表明，Nap-GFFYG-RGD 肽自组装纳米纤维是一种有前途的用于癌症靶向治疗的疏水性药物递送系统。
