期刊
BIOCONJUGATE CHEMISTRY
卷 18, 期 1, 页码 101-108出版社
AMER CHEMICAL SOC
DOI: 10.1021/bc060174r
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- NCI NIH HHS [R01 CA098945-01A1, R01 CA098945, P30 CA016058, R01 CA098945-04, R01 CA098945-02, P30CA16058, R01 CA098945-03, 1 R01-CA098945] Funding Source: Medline
- NATIONAL CANCER INSTITUTE [R01CA098945, P30CA016058] Funding Source: NIH RePORTER
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, mPEG(2000)-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 F98(EGFR) 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 (similar to 8-fold) cellular uptake of boron was obtained using cetuximab-ILs in EGFR(+) F98(EGFR) 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.
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