期刊
JOURNAL OF CONTROLLED RELEASE
卷 157, 期 1, 页码 118-125出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2011.07.034
关键词
LyP-1; Liposomes; Targeted therapy; Doxorubicin; Lymphatic metastatic tumors
资金
- National Science and Technology Major Project of China [2009ZX09310-006]
- National Basic Research Program of China (973 Program) [2010CB934000]
- National Natural Science Foundation of China [81072593]
The application of liposomes in targeted therapy of lymphatic metastatic tumors has been hampered by the low uptake rate of liposome by metastatic lymph nodes. In this report, LyP-1, a peptide that can specifically bind tumor cells, tumor lymphatics and tumor-associated macrophages, was conjugated to liposomes for targeting and treating lymphatic metastatic tumors. Firstly, LyP-1-conjugated PEGylated liposomes loaded with fluorescein or doxorubicin (DOX) were prepared and showed satisfactory vesicle size and size distribution. The in vitro cellular uptake and in vivo near-infrared fluorescence imaging results showed that LyP-1 modification increased liposome uptake by tumor cells and metastatic lymph nodes, but did not increase uptake by normal lymph nodes. The immunofluorescence analysis evidenced that LyP-1-conjugated liposomes were distributed adjacent to tumor lymphatics and tumor-associated macrophages in metastatic lymph nodes. The pharmacodynamic study suggested that compared with unmodified liposomes, LyP-1-conjugated DOX-loaded liposomes exhibited enhanced inhibition effect on tumor cells in vitro and lymphatic metastatic tumors in vivo. Pathological examination showed that liposomal DOX caused reduced tissue damage to injection site compared with DOX solution. In summary, LyP-1-conjugated PEGylated liposomes could be targeted to metastatic lymph nodes based on their specific binding to tumor cells, tumor lymphatics and tumor-associated macrophages. They are a safe and effective drug delivery system of antineoplastic agents for targeted therapy of lymphatic metastatic tumors. (C) 2011 Elsevier B.V. All rights reserved.
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