Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing, People's Republic of China.
Int J Nanomedicine. 2013;8:2473-85. doi: 10.2147/IJN.S46962. Epub 2013 Jul 15.
Considering the fact that iRGD (tumor-homing peptide) demonstrates tumor-targeting and tumor-penetrating activity, and that B16-F10 (murine melanoma) cells overexpress both αv integrin receptor and neuropilin-1 (NRP-1), the purpose of this study was to prepare a novel doxorubicin (DOX)-loaded, iRGD-modified, sterically-stabilized liposome (SSL) (iRGD-SSL-DOX) in order to evaluate its antitumor activity on B16-F10 melanoma cells in vitro and in vivo. The iRGD-SSL-DOX was prepared using a thin-film hydration method. The characteristics of iRGD-SSL-DOX were evaluated. The in vitro leakage of DOX from iRGD-SSL-DOX was tested. The in vitro tumor-targeting and tumor-penetrating characteristics of iRGD-modified liposomes on B16-F10 cells were investigated. The in vivo tumor-targeting and tumor-penetrating activities of iRGD-modified liposomes were performed in B16-F10 tumor-bearing nude mice. The antitumor effect of iRGD-SSL-DOX was evaluated in B16-F10 tumor-bearing C57BL/6 mice in vivo. The average particle size of the iRGD-SSL-DOX was found to be 91 nm with a polydispersity index (PDI) of 0.16. The entrapment efficiency of iRGD-SSL-DOX was 98.36%. The leakage of DOX from iRGD-SSL-DOX at the 24-hour time point was only 7.5%. The results obtained from the in vitro flow cytometry and confocal microscopy, as well as in vivo biodistribution and confocal immunofluorescence microscopy experiments, indicate that the tumor-targeting and tumor-penetrating activity of the iRGD-modified SSL was higher than that of unmodified SSL. In vivo antitumor activity results showed that the antitumor effect of iRGD-SSL-DOX against melanoma tumors was higher than that of SSL-DOX in B16-F10 tumor-bearing mice. In conclusion, the iRGD-SSL-DOX is a tumor-targeting and tumor-penetrating peptide modified liposome which has significant antitumor activity against melanoma tumors.
考虑到 iRGD（肿瘤归巢肽）具有肿瘤靶向和肿瘤穿透活性，并且 B16-F10（小鼠黑色素瘤）细胞过度表达 αv 整联蛋白受体和神经纤毛蛋白-1（NRP-1），本研究旨在制备一种新型阿霉素（DOX）负载、iRGD 修饰、空间稳定化脂质体（SSL）（iRGD-SSL-DOX），以评估其在体外和体内对 B16-F10 黑色素瘤细胞的抗肿瘤活性。iRGD-SSL-DOX 通过薄膜水化法制备。评价 iRGD-SSL-DOX 的特性。测试 DOX 从 iRGD-SSL-DOX 中的体外泄漏。研究 iRGD 修饰的脂质体对 B16-F10 细胞的体外肿瘤靶向和肿瘤穿透特性。在 B16-F10 荷瘤裸鼠中进行 iRGD 修饰的脂质体的体内肿瘤靶向和肿瘤穿透活性。在体内评价 iRGD-SSL-DOX 对 B16-F10 荷瘤 C57BL/6 小鼠的抗肿瘤作用。iRGD-SSL-DOX 的平均粒径为 91nm，多分散指数（PDI）为 0.16。iRGD-SSL-DOX 的包封效率为 98.36%。24 小时时 DOX 从 iRGD-SSL-DOX 的泄漏率仅为 7.5%。体外流式细胞术和共聚焦显微镜、体内生物分布和共聚焦免疫荧光显微镜实验的结果表明，iRGD 修饰的 SSL 的肿瘤靶向和肿瘤穿透活性高于未修饰的 SSL。体内抗肿瘤活性结果表明，iRGD-SSL-DOX 对黑色素瘤肿瘤的抗肿瘤作用高于 SSL-DOX 在 B16-F10 荷瘤小鼠中的作用。总之，iRGD-SSL-DOX 是一种肿瘤靶向和肿瘤穿透肽修饰的脂质体，对黑色素瘤肿瘤具有显著的抗肿瘤活性。
