title: Design of a tumor-homing cell-penetrating peptide.
abstract: Chemotherapy is often limited by toxicity to normal cells. Therefore, an ideal anticancer drug should discriminate between normal tissue and tumors. This would require a target receptor molecule mostly present in tumors. The cyclic peptide cCPGPEGAGC (PEGA) is a homing peptide that has previously been shown to accumulate in breast tumor tissue in mice. PEGA peptide does not cross the plasma membrane per se; however, when attached to the cell-penetrating peptide pVEC, the conjugate is taken up by different breast cancer cells in vitro. Additionally, the homing capacity of the PEGA- pVEC is conserved in vivo, where the conjugate mainly accumulates in blood vessels in breast tumor tissue and, consequently is taken up. Furthermore, we show that the efficacy of the anticancer drug, chlorambucil, is increased more than 4 times when the drug is conjugated to the PEGA- pVEC chimeric peptide. These data demonstrate that combining a homing sequence with a cell-penetrating sequence yields a peptide that combines the desirable properties of the parent peptides. Such peptides may be useful in diagnostics and delivery of therapeutic agents to an intracellular location in a specific tumor target tissue.
authors.affiliation: Department of Neurochemistry, Stockholm University, Svante Arrhenius väg 21A, SE-106 91 Stockholm, Sweden. helenam@neurochem.su.se
authors.forename: Helena
authors.initials: H
authors.lastname: Myrberg
authors.forename: Lianglin
authors.initials: L
authors.lastname: Zhang
authors.forename: Maarja
authors.initials: M
authors.lastname: Mäe
authors.forename: Ulo
authors.initials: U
authors.lastname: Langel
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D002699:Chlorambucil / Q000737:chemistry / Q000494:pharmacology; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D015195:Drug Design; D005260:Female; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009928:Organ Specificity; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D010456:Peptides, Cyclic / Q000737:chemistry / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D010455:Peptides; D010456:Peptides, Cyclic; C437783:pVEC peptide; D002699:Chlorambucil