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Nanomedicine (Lond). 2010 Jun;5(4):563-74. doi: 10.2217/nnm.10.30.

Enhanced binding and killing of target tumor cells by drug-loaded liposomes modified with tumor-specific phage fusion coat protein.

Author information

1
Department of Pharmaceutical Sciences & Center for Pharmaceutical Biotechnology & Nanomedicine, Northeastern University, Boston, MA 02115, USA.

Abstract

AIM:

To explore cancer cell-specific phage fusion pVIII coat protein, identified using phage display, for targeted delivery of drug-loaded liposomes to MCF-7 breast cancer cells.

MATERIAL & METHODS:

An 8-mer landscape library f8/8 and a biopanning protocol against MCF-7 cells were used to select a landscape phage protein bearing MCF-7-specific peptide. Size and morphology of doxorubicin-loaded liposomes modified with the tumor-specific phage fusion coat protein (phage-Doxil) were determined by dynamic light scattering and freeze-fraction electron microscopy. Topology of the phage protein in liposomes was examined by western blot. Association of phage-Doxil with MCF-7 cells was evaluated by fluorescence microscopy and fluorescence spectrometry. Selective targeting to MCF-7 was shown by FACS using a coculture model with target and nontarget cells. Phage-Doxil-induced tumor cell killing and apoptosis were confirmed by CellTiter-Blue Assay and caspase-3/CPP32 fluorometric assay.

RESULTS:

A chimeric phage fusion coat protein specific towards MCF-7 cells, identified from a phage landscape library, was directly incorporated into the liposomal bilayer of doxorubicin-loaded PEGylated liposomes (Doxil) without additional conjugation with lipophilic moieties. Western blotting confirmed the presence of both targeting peptide and pVIII coat protein in the phage-Doxil, which maintained the liposomal morphology and retained a substantial part of the incorporated drug after phage protein incorporation. The binding activity of the phage fusion pVIII coat protein was retained after incorporation into liposomes, and phage-Doxil strongly and specifically targeted MCF-7 cells, demonstrating significantly increased cytotoxicity towards target cells in vitro.

CONCLUSION:

We present a novel and straightforward method for making tumor-targeted nanomedicines by anchoring specific phage proteins (substitute antibodies) on their surface.

PMID:
20528452
PMCID:
PMC2914609
DOI:
10.2217/nnm.10.30
[Indexed for MEDLINE]
Free PMC Article
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