title: Selective gene delivery to cancer cells using an integrated cationic amphiphilic peptide.
abstract: Gene therapy provides a number of potential treatments that could be applied in clinic to prevent deaths from cancer. However, the transfer of gene therapy to the clinical application has proven difficult because many problems remain to be solved concerning the transfection efficiency, target specificity, and safety issues. To overcome these barriers, a peptide-based vector, K(12)H(6)V(8)SSQHWSYKLRP (KHV-LHRH) that comprises four functional blocks, is studied in this work for the targeted delivery of a model gene drug to cancer cells. KHV-LHRH peptide, which contains a luteinizing hormone-releasing hormone (LHRH) sequence, can specifically target cancer cells expressing LHRH receptors. The gene expression, cytotoxicity, and cellular uptake mediated by this vector were evaluated against MCF-7 human breast cancer cells (LHRH-receptor-positive) and SKOV-3 human ovarian carcinoma cells (LHRH-receptor-negative) and compared to a peptide vector (K(12)H(6)V(8)) (KHV) without the LHRH ligand and poly(ethylenimine) (PEI). The results showed that KHV-LHRH enhanced the DNA internalization and induced significantly higher gene expression than KHV in LHRH-receptor-positive MCF-7 cells. Also, the peptide-based vectors had low cytotoxicity compared to that of PEI. The high specificity and transfection efficiency of the integrated peptide-based vector make it a very promising material for targeted gene delivery in cancer therapy.
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Akron, Akron, Ohio 44325, United States.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Tang
authors.forename: Bin
authors.initials: B
authors.lastname: Cao
authors.forename: Haiyan
authors.initials: H
authors.lastname: Wu
authors.forename: Gang
authors.initials: G
authors.lastname: Cheng
mesh_terms: D000595:Amino Acid Sequence; D001943:Breast Neoplasms / Q000235:genetics; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000493:pharmacokinetics; D004354:Drug Screening Assays, Antitumor; D005260:Female; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000008:administration & dosage / Q000493:pharmacokinetics; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D010051:Ovarian Neoplasms / Q000235:genetics; D010316:Particle Size; D010455:Peptides / Q000008:administration & dosage* / Q000235:genetics* / Q000493:pharmacokinetics; D011094:Polyethyleneimine / Q000008:administration & dosage / Q000737:chemistry; D014162:Transfection
chemical_list: D004337:Drug Carriers; D010455:Peptides; D007987:Gonadotropin-Releasing Hormone; D011094:Polyethyleneimine