Synthesis of cetuximab-immunoliposomes via a cholesterol-based membrane anchor for targeting of EGFR.

Abstract	The objective of the present study was to construct epidermal growth factor receptor (EGFR) targeting cetuximab-immunoliposomes (ILs) for targeted delivery of boron compounds to EGFR(+) glioma cells for neutron capture therapy. The ILs were synthesized by using a novel cholesterol-based membrane anchor, maleimido-PEG-cholesterol (Mal-PEG-Chol), to incorporate cetuximab into liposomes by either surface conjugation or a post-insertion method. For post-insertion, the transfer efficiency of MAb conjugates from micelles to liposome was examined at varying temperatures, mPEG2000-DSPE ratios, and micelle-to-liposome lipid ratios. Following this, the cetuximab-ILs were evaluated for targeted delivery of the encapsulated boron anion, dodecahydro-closo-dodecaborate (2-) (B12H122-), to human EGFR gene transfected F98EGFR glioma cells as potential delivery agents for boron neutron capture therapy (BNCT). In addition, cellular uptake of cetuximab-ILs, encapsulating a fluorescence dye, was analyzed by confocal fluorescence microscopy and flow cytometry, and boron content was quantified by ICP-MS. Much greater ( approximately 8-fold) cellular uptake of boron was obtained using cetuximab-ILs in EGFR(+) F98EGFR compared with nontargeted human IgG-ILs. On the basis of these observations, we have concluded that cholesterol can serve as an effective anchor for MAb in liposomes, and cetuximab-ILs are potentially useful delivery vehicles for BNCT of gliomas.
Authors	Xiaogang Pan, Gong Wu, Weiliang Yang, Rolf F Barth, Werner Tjarks, Robert J Lee
Journal	Bioconjugate chemistry (Bioconjug Chem) 2007 Jan-Feb Vol. 18 Issue 1 Pg. 101-8 ISSN: 1043-1802 [Print] United States
PMID	17226962 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
Chemical References	Antibodies, Monoclonal Antibodies, Monoclonal, Humanized Liposomes Micelles Cholesterol ErbB Receptors Cetuximab
Topics	Antibodies, Monoclonal (immunology) Antibodies, Monoclonal, Humanized Cell Line, Tumor Cetuximab Cholesterol (chemistry) ErbB Receptors (immunology) Humans Kinetics Liposomes Micelles Molecular Structure

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