LyP-1-conjugated doxorubicin-loaded liposomes suppress lymphatic metastasis by inhibiting lymph node metastases and destroying tumor lymphatics
LyP-1-conjugated doxorubicin-loaded liposomes suppress lymphatic metastasis by inhibiting lymph node metastases and destroying tumor lymphatics
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DOI：
10.1088/0957-4484/22/41/415103
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发表时间：
2011-10-14
期刊：
影响因子：
3.5
通讯作者：
Lu, Weiyue
中科院分区：
文献类型：
--
作者：
Yan, Zhiqiang;Zhan, Changyou;Lu, Weiyue
淋巴结中的转移瘤生长和淋巴管生成可极大地促进淋巴转移。LyP-1是一种环肽，能够特异性地与转移性淋巴结中的肿瘤细胞和肿瘤代谢物结合。本工作旨在使用负载阿霉素（DOX）的LyP-1缀合脂质体（L-LS）（L-LS/DOX）通过抑制淋巴结中的转移和肿瘤增殖来抑制淋巴结转移。L-LS的制备，并表现出约90 nm的尺寸和球形形态，其特征在于通过透射电子显微镜。体外细胞实验表明，LyP-1修饰后的脂质体能明显增加MDA-MB-435肿瘤细胞对脂质体的摄取，增强脂质体阿霉素的细胞毒作用。采用裸鼠皮下接种肿瘤细胞的方法成功建立了腘、髂淋巴结转移模型。免疫荧光染色分析表明，LyP-1修饰后脂质体与肿瘤细胞特异性结合，增强了脂质体DOX对肿瘤细胞的杀伤作用。体内荧光成像和药效学研究表明，LyP-1修饰增加了转移性LN的脂质体摄取，L-LS/DOX显著降低了转移性LN的生长和LN转移率。这些结果表明，L-LS/DOX是一种有效的抑制淋巴结转移的给药系统，同时抑制LN转移和肿瘤浸润。
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.