Cell-specific delivery of a chemotherapeutic to lung cancer cells.
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.
Zhou
Xin
X
Center for Biomedical Inventions and Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9185, USA.
Chang
Ya-Ching
YC
Oyama
Tsukasa
T
McGuire
Michael J
MJ
Brown
Kathlynn C
KC
D000595:Amino Acid Sequence; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000008:administration & dosage / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D008969:Molecular Sequence Data; D010455:Peptides / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000493:pharmacokinetics
D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D010455:Peptides; D004317:Doxorubicin