Antitumor Effect of Paclitaxel-Loaded PEGylated Immunoliposomes Against Human Breast Cancer Cells |
| |
Authors: | Tao Yang Min-Koo Choi Fu-De Cui Seung-Jin Lee Suk-Jae Chung Chang-Koo Shim Dae-Duk Kim |
| |
Institution: | (1) College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, People’s Republic of China;(2) College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 151-742, South Korea;(3) College of Pharmacy, Ewha Womans University, Seoul, 120-750, South Korea |
| |
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. |
| |
Keywords: | antitumor effect herceptin paclitaxel PEGylated immunoliposome |
本文献已被 PubMed SpringerLink 等数据库收录! |
|