Tumor-targeted PE38KDEL delivery via PEGylated anti-HER2 immunoliposomes - PubMed (original) (raw)

Comparative Study

. 2009 Jun 5;374(1-2):145-52.

doi: 10.1016/j.ijpharm.2009.03.018. Epub 2009 Mar 24.

Wei Zhong, Jinqiu He, Huimei Li, He Zhang, Guichen Zhou, Bohua Li, Ying Lu, Hao Zou, Geng Kou, Dapeng Zhang, Hao Wang, Yajun Guo, Yanqiang Zhong

Affiliations

• PMID: 19446771
• DOI: 10.1016/j.ijpharm.2009.03.018

Comparative Study

Tumor-targeted PE38KDEL delivery via PEGylated anti-HER2 immunoliposomes

Jie Gao et al. Int J Pharm. 2009.

Abstract

We previously reported the development of PE38KDEL-loaded anti-HER2 poly(lactic-co-glycolic acid) (PLGA) nanoparticles that bind and internalize in HER2-overexpressing breast cancer cells, enabling potent anti-tumor activity. To overcome the problems associated with the short half-lives of this drug delivery system, we have constructed PE38KDEL-loaded anti-HER2 PEGylated liposomes (PE-HER-liposomes). PE-HER-liposomes were constructed with Fab' of recombinant humanized anti-HER2 monoclonal antibody (anti-HER2 Fab') covalently linked to PEGylated liposomes containing PE38KDEL (PE-liposomes). We attached anti-HER2 Fab' to the terminus of PEG (polyethylene glycol) on PEGylated liposomes. Incorporation of pyridylthiopropionoylamino-PEG-distearoylphosphatidylethanolamine (PDP-PEG-DSPE) into PEGylated liposomes followed by mild thiolysis of the PDP groups resulted in the formation of reactive thiol groups at the periphery of the liposomes. Efficient attachment of maleimide-derivatized anti-HER2 Fab' took place under mild conditions. The characterization of PE-HER-liposomes, such as particle size, was evaluated by dynamic light-scattering detector. The Micro BCA method was used to determine the encapsulation efficiency of PE38KDEL and the quantity of conjugated Fab'. Flow cytometry and confocal microscopy showed that PE-HER-liposomes possessed receptor-specific binding and internalization for HER2-overexpressing SK-BR3 cells. Remarkably, PE-HER-liposomes were more cytotoxic than non-targeted PE-liposomes in HER2-overexpressing breast cancer cells. In conclusion, PE-HER-liposomes could serve as a promising therapeutic candidate for the treatment of HER2-overexpressing breast cancers.

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