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Nanomedicine. 2014 Feb;10(2):421-30. doi: 10.1016/j.nano.2013.08.009. Epub 2013 Sep 9.

Enhanced tumor delivery and antitumor activity in vivo of liposomal doxorubicin modified with MCF-7-specific phage fusion protein.

Author information

1
Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston, MA, USA.
2
Department of Pathobiology, College of Veterinary Medicine, Auburn University, AL, USA.
3
Center for Translational Imaging, Northeastern University, Boston, MA, USA.
4
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
5
Department of Biology, College of Science, Northeastern University, Boston, MA, USA.
6
Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston, MA, USA. Electronic address: v.torchilin@neu.edu.

Abstract

A novel strategy to improve the therapeutic index of chemotherapy has been developed by the integration of nanotechnology with phage technique. The objective of this study was to combine phage display, identifying tumor-targeting ligands, with a liposomal nanocarrier for targeted delivery of doxorubicin. Following the proof of concept in cell-based experiments, this study focused on in vivo assessment of antitumor activity and potential side-effects of phage fusion protein-modified liposomal doxorubicin. MCF-7-targeted phage-Doxil treatments led to greater tumor remission and faster onset of antitumor activity than the treatments with non-targeted formulations. The enhanced anticancer effect induced by the targeted phage-Doxil correlated with an improved tumor accumulation of doxorubicin. Tumor sections consistently revealed enhanced apoptosis, reduced proliferation activity and extensive necrosis. Phage-Doxil-treated mice did not show any sign of hepatotoxicity and maintained overall health. Therefore, MCF-7-targeted phage-Doxil seems to be an active and tolerable chemotherapy for breast cancer treatment.

FROM THE CLINICAL EDITOR:

The authors of this study successfully combined phage display with a liposomal nanocarrier for targeted delivery of doxorubicin using MCF-7-targeted phage-Doxil nanocarriers in a rodent model. The method demonstrated improved efficiency and reduced hepatotoxicity, paving the way to future clinical trials addressing breast cancer.

KEYWORDS:

Breast cancer targeting; Cancer nanomedicines; Drug delivery; Liposomes; Phage display

PMID:
24028893
PMCID:
PMC3946195
DOI:
10.1016/j.nano.2013.08.009
[Indexed for MEDLINE]
Free PMC Article

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