Key Laboratory of Smart Drug Delivery, Ministry of Education and PLA, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, People's Republic of China.
Nanotechnology. 2011 Oct 14;22(41):415103. doi: 10.1088/0957-4484/22/41/415103. Epub 2011 Sep 14.
Lymphatic metastasis can be greatly promoted by metastases growth and lymphangiogenesis in lymph nodes (LNs). LyP-1, a cyclic peptide, is able to specifically bind with tumor cells and tumor lymphatics in metastatic LNs. This work aimed to use LyP-1-conjugated liposomes (L-LS) loaded with doxorubicin (DOX) (L-LS/DOX) to suppress lymphatic metastasis by inhibiting both metastases and tumor lymphatics in LNs. L-LS were prepared and exhibited sizes around 90 nm and spherical morphology as characterized by transmission electron microscopy. The in vitro cellular studies showed that LyP-1 modification obviously increased liposome uptake by MDA-MB-435 tumor cells and enhanced the cytotoxicity of liposomal DOX. A popliteal and iliac LN metastases model was successfully established by subcutaneous inoculation of tumor cells to nude mice. The immunofluorescence staining analysis indicated that LyP-1 modification enabled specific binding of liposome with tumor lymphatics and enhanced the destroying effect of liposomal DOX on tumor lymphatics. The in vivo fluorescence imaging and pharmacodynamic studies showed that LyP-1 modification increased liposome uptake by metastatic LNs and that L-LS/DOX significantly decreased metastatic LN growth and LN metastasis rate. These results suggested that L-LS/DOX were an effective delivery system for suppressing lymphatic metastasis by simultaneously inhibiting LN metastases and tumor lymphatics.
淋巴转移可以通过转移生长和淋巴结（LNs）中的淋巴管生成得到极大地促进。一种环状肽 LyP-1 能够特异性地与转移 LNs 中的肿瘤细胞和肿瘤淋巴管结合。本工作旨在使用 LyP-1 缀合的载多柔比星（DOX）的脂质体（L-LS/DOX）通过抑制 LNs 中的转移和肿瘤淋巴管来抑制淋巴转移。L-LS 通过透射电子显微镜进行表征，结果表明其粒径约为 90nm 并呈现球形形态。体外细胞研究表明，LyP-1 修饰明显增加了 MDA-MB-435 肿瘤细胞对脂质体的摄取，并增强了脂质体 DOX 的细胞毒性。通过将肿瘤细胞皮下接种到裸鼠中来成功建立了后肢和髂淋巴结转移模型。免疫荧光染色分析表明，LyP-1 修饰能够使脂质体与肿瘤淋巴管特异性结合，并增强脂质体 DOX 对肿瘤淋巴管的破坏作用。体内荧光成像和药效学研究表明，LyP-1 修饰增加了转移 LNs 对脂质体的摄取，而 L-LS/DOX 显著降低了转移 LNs 的生长和 LNs 的转移率。这些结果表明，L-LS/DOX 是一种通过同时抑制 LN 转移和肿瘤淋巴管来抑制淋巴转移的有效递送系统。
