NDLI: Antitumor Effect of Paclitaxel-Loaded PEGylated Immunoliposomes Against Human Breast Cancer Cells

Content Provider	Springer Nature Link
Author	Yang, Tao Choi, Min Koo Cui, Fu De Lee, Seung Jin Chung, Suk Jae Shim, Chang Koo Kim, Dae Duk
Copyright Year	2007
Abstract	The antitumor effect of paclitaxel-loaded PEGylated immunoliposome (PILs) was investigated in breast cancer cell lines and the xenograft model.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.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.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.
Starting Page	2402
Ending Page	2411
Page Count	10
File Format	PDF
ISSN	07248741
Journal	Pharmaceutical Research
Volume Number	24
Issue Number	12
e-ISSN	1573904X
Language	English
Publisher	Springer US
Publisher Date	2007-09-09
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	antitumor effect herceptin paclitaxel PEGylated immunoliposome Biomedical Engineering Medical Law Biochemistry Pharmacy Pharmacology/Toxicology
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Pharmacology Molecular Medicine Pharmacology (medical) Biotechnology Pharmaceutical Science

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