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Antitumor effect of paclitaxel-loaded PEGylated immunoliposomes against human breast cancer cells

Title
Antitumor effect of paclitaxel-loaded PEGylated immunoliposomes against human breast cancer cells
Authors
Yang T.Choi M.-K.Cui F.-D.Lee S.-J.Chung S.-J.Shim C.-K.Kim D.-D.
Ewha Authors
이승진
SCOPUS Author ID
이승진scopus
Issue Date
2007
Journal Title
Pharmaceutical Research
ISSN
0724-8741JCR Link
Citation
vol. 24, no. 12, pp. 2402 - 2411
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Purpose. The antitumor effect of paclitaxel-loaded PEGylated immunoliposome (PILs) was investigated in breast cancer cell lines and the xenograft model. Methods. Herceptin was conjugated to paclitaxel-loaded PEGylated liposomes (PLs). In vitro cellular uptake and cytotoxicity of PILs were determined in breast cancer cell lines while in vivo antitumor efficacy was evaluated in the xenograft nude mouse model. Results. The PILs formulation was able to significantly increase the HER2 mediated cellular uptake of paclitaxel compared to the PLs in cell lines overexpressing HER2 (BT-474 and SK-BR-3 cells). However, in the MDA-MB-231 cells, which express low levels of HER2, the difference between the PILs and PLs formulation was not significant. The biological activity of Herceptin was maintained throughout the conjugation process as exhibited by the antitumor dose-response curves determined for Herceptin itself, for the thiolated Herceptin alone and subsequently for the immunoliposome-coupled Herceptin. In BT-474 and SK-BR-3 cells, the cytotoxicity of the PILs was more potent than that of Taxol. Moreover, in in vivo studies, PILs showed significantly higher tumor tissue distribution of paclitaxel in the BT-474 xenograft model and more superior antitumor efficacy compared to Taxol and PLs. However, in the MDA-MB-231 xenograft model, PILs and PLs showed similar tumor tissue distribution as well as antitumor activity. Conclusions. These results suggest that HER2-mediated endocytosis is involved in the PILs formulation. The ability of the PILs formulation to efficiently and specifically deliver paclitaxel to the HER2-overexpressing cancer cells implies that it is a promising strategy for tumor-specific therapy for HER2-overexpressing breast cancers. © 2007 Springer Science+Business Media, LLC.
DOI
10.1007/s11095-007-9425-y
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약학대학 > 약학과 > Journal papers
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