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The Improved Delivery to Breast Cancer Based on a Novel Nanocarrier Modified with High-Affinity Peptides Discovered by Phage Display.
Advanced Healthcare Materials 2018 October
Ligand-targeted nanosystems have the potential to realize site-specific tumor therapy and alleviate unwanted side effects of many chemotherapeutic agents, and one of the most key issues seems to be the construction of an effective nanocarrier. Based on different processes of phage display techniques, 38 cell-binding peptides and 32 cell-internalizing peptides are discovered. Four of these ligand peptides [FIPFDPMSMRWE (FIP), NASSFPTNSRWA (NAS), GLHTSATNLYLH (GLH), and ALAVAPSRWWNE (ALA), respectively] exhibit high affinity to MCF7 human breast cancer cells. Among them, NAS and ALA are reported for the first time, whose affinities are 20.6 and 76.3 times that of the random peptide control, respectively. Both NAS and ALA modifications to doxorubicin-loaded lipid nanosytems [LP(DOX)] show stronger tumor inhibition, longer animal survival time, and less body weight loss, compared to unmodified or control peptide modified nanosystems, on an MCF7 tumor-bearing mouse model. In conclusion, the cell-binding peptide NAS and cell-internalizing peptide ALA can be used for ligand-targeted delivery of antitumor drugs. It seems that the in vivo antitumor effect of these ligand-targeted nanosystems is closely related to their ligand-cell affinity, but fairly tolerant of the ligand types.
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