Cell-Specific Delivery of a Chemotherapeutic to Lung Cancer Cells

Center for Biomedical Inventions and Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9185, USA.
Journal of the American Chemical Society (Impact Factor: 12.11). 01/2005; 126(48):15656-7. DOI: 10.1021/ja0446496
Source: PubMed


We report that lung cancer-targeting peptides isolated from a peptide library can be used to deliver an active chemotherapeutic in a cell-specific fashion. The peptides were removed from the context of the phage and placed on a pegylated tetrameric scaffold. The tetrameric peptides were shown to block uptake of their cognate phage. The tetrameric peptides were coupled to doxorubicin, and their cytotoxicity against a panel of different cell lines was tested. Our data demonstrate that these targeting peptides can deliver an active anticancer agent in a cell-specific fashion, resulting in an increase of the therapeutic index of the targeted drug compared to systemic delivery. The efficacy of the peptide conjugate correlates to the affinity of the targeting peptide for a particular cell line. As such, we have demonstrated that cell-specific targeted drugs can be synthesized, even when the cell surface target is unknown.

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    • "We have previously isolated a peptide that binds to the large cell lung carcinoma cell line, H1299 (Oyama et al., 2003). This peptide, named TP H1299.1, has the sequence VSQTM- RQTAVPLLWFWTGSL and has been shown to be useful for cell-specific drug delivery (Zhou et al., 2004). Here we report the construction of a new 20-mer peptide-phage library and the isolation of a new peptide that binds to the H1299 cell line. "
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