Apoptotic epidermal growth factor (EGF)-conjugated block copolymer micelles as a nanotechnology platform for targeted combination therapy.

Apoptotic epidermal growth factor (EGF)-conjugated block copolymer micelles as a nanotechnology platform for targeted combination therapy. Research Abstract Details 

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Apoptotic epidermal growth factor (EGF)-conjugated block copolymer micelles as a nanotechnology platform for targeted combination therapy. Abstract Text:

Helen Lee,Meiduo Hu,Raymond M Reilly,Christine Allen,Helen Lee,Meiduo Hu,Raymond M Reilly,Christine Allen,

The overexpression of epidermal growth factor receptor (EGFR) in human epithelial cancers has been associated with aggressive disease, poor patient prognosis, and a high incidence of metastases. In the present study, block copolymer micelles are conjugated with epidermal growth factor (EGF), which acts as both a targeting ligand for the drug carrier and an apoptotic factor against EGFR-overexpressing cancers. Drug-free EGF-conjugated micelles are shown to result in cell-cycle arrest at the G 1 phase and subsequent induction of cell-type-specific apoptosis in EGFR-overexpressing breast cancer cells as demonstrated by flow cytometric analysis. EGF delivered as EGF-conjugated micelles was found to be 13-fold more potent than free EGF; the IC 50 was decreased from 0.98 +/- 0.1 nM for free EGF to 0.076 +/- 0.01 nM for EGF micelles. The apoptotic micelles, however, are non-antiproliferative to cells expressing a low level of EGFR, suggesting that the apoptotic micelles have minimal or no toxicity against normal healthy tissues. Ellipticine, a chemotherapeutic agent, was loaded into the EGF-micelles after it had been shown, using the combination index-isobologram equation, to act synergistically with EGF. A 10-fold increase in EGF content in the ellipticine-loaded micelles lowered the IC 50 of ellipticine in EGFR-overexpressing breast cancer cells by more than 18-fold. The EGF-micelles have the potential to be further pursued as a versatile nanotechnology platform for targeted delivery of a wide range of chemotherapeutic agents as a combination therapy for the treatment of EGFR-overexpressing cancers.

Apoptotic epidermal growth factor (EGF)-conjugated block copolymer micelles as a nanotechnology platform for targeted combination therapy. Publishing Authors By Initials

H Lee,M Hu,RM Reilly,C Allen,H Lee,M Hu,RM Reilly,C Allen,

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Apoptotic epidermal growth factor (EGF)-conjugated block copolymer micelles as a nanotechnology platform for targeted combination therapy. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Molecular pharmaceutics

VOLUME: 4

Page Numbers: 769-81

Journal Abbreviation: Mol. Pharm.

ISSN: 1543-8384

DAY: 15

MONTH: 09

YEAR: 2007

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LANGUAGE: eng

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AFFILIATION: Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, Division of Nuclear Medicine, University Health Network, University of Toronto, 144 College Street, Toronto, Ontario, Canada.

Country: United States

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MEDLINETA: Mol Pharm

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