Pharmaceutical Research

, Volume 24, Issue 12, pp 2402–2411 | Cite as

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

  • Tao Yang
  • Min-Koo Choi
  • Fu-De Cui
  • Seung-Jin Lee
  • Suk-Jae Chung
  • Chang-Koo Shim
  • Dae-Duk Kim
Research Paper



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.

Key words

antitumor effect herceptin paclitaxel PEGylated immunoliposome 





Dulbecco’s modified eagle medium


enhanced permeability and retention


fetal bovine serum


human epidermal growth factor receptor-2


minimum essential medium


1,2-distearoyl-sn-glycero-3-phosphoethanolamine [methoxy(polyethyleneglycol)-2000]


3-(4,5-dimethylthiazol-2-ly)– 2,5-diphenyl-tetrazolium bromide


phosphate-buffered saline


polyethylene glycol


PEGylated immunoliposomes


PEGylated liposomes


soybean phosphatidylcholine


rhodamine labeled-phosphatidylethanolamine



This research was financially supported by the Ministry of Science and Technology (M10528010004-06N2801-00410) in Korea. The authors would like to thank the Lipoid GmbH (Germany) and Genentech companies for providing phosphatidylcholine and Herceptin, respectively.


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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Tao Yang
    • 1
    • 2
  • Min-Koo Choi
    • 2
  • Fu-De Cui
    • 1
  • Seung-Jin Lee
    • 3
  • Suk-Jae Chung
    • 2
  • Chang-Koo Shim
    • 2
  • Dae-Duk Kim
    • 2
  1. 1.College of PharmacyShenyang Pharmaceutical UniversityShenyangPeople’s Republic of China
  2. 2.College of Pharmacy and Research Institute of Pharmaceutical SciencesSeoul National UniversitySeoulSouth Korea
  3. 3.College of PharmacyEwha Womans UniversitySeoulSouth Korea

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