title: Synergistic gene and drug tumor therapy using a chimeric peptide.
abstract: Co-delivery of gene and drug for synergistic therapy has provided a promising strategy to cure devastating diseases. Here, an amphiphilic chimeric peptide (Fmoc)2KH7-TAT with pH-responsibility for gene and drug delivery was designed and fabricated. As a drug carrier, the micelles self-assembled from the peptide exhibited a much faster doxorubicin (DOX) release rate at pH 5.0 than that at pH 7.4. As a non-viral gene vector, (Fmoc)(2)KH(7)-TAT peptide could satisfactorily mediate transfection of pGL-3 reporter plasmid with or without the existence of serum in both 293T and HeLa cell-lines. Besides, the endosome escape capability of peptide/DNA complexes was investigated by confocal laser scanning microscopy (CLSM). To evaluate the co-delivery efficiency and the synergistic anti-tumor effect of gene and drug, p53 plasmid and DOX were simultaneously loaded in the peptide micelles to form micelleplexes during the self-assembly of the peptide. Cellular uptake and intracellular delivery of gene and drug were studied by CLSM and flow cytometry respectively. And p53 protein expression was determined via Western blot analysis. The in vitro cytotoxicity and in vivo tumor inhibition effect were also studied. Results suggest that the co-delivery of gene and drug from peptide micelles resulted in effective cell growth inhibition in vitro and significant tumor growth restraining in vivo. The chimeric peptide-based gene and drug co-delivery system will find great potential for tumor therapy.
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education and Department of Chemistry, Wuhan University, Wuhan 430072, PR China.
authors.forename: Kai
authors.initials: K
authors.lastname: Han
authors.forename: Si
authors.initials: S
authors.lastname: Chen
authors.forename: Wei-Hai
authors.initials: WH
authors.lastname: Chen
authors.forename: Qi
authors.initials: Q
authors.lastname: Lei
authors.forename: Yun
authors.initials: Y
authors.lastname: Liu
authors.forename: Ren-Xi
authors.initials: RX
authors.lastname: Zhuo
authors.forename: Xian-Zheng
authors.initials: XZ
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000627:therapeutic use; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics / Q000627:therapeutic use; D004317:Doxorubicin / Q000008:administration & dosage* / Q000627:therapeutic use; D004337:Drug Carriers / Q000737:chemistry*; D005449:Fluorenes / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008823:Micelles; D009369:Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D010455:Peptides / Q000737:chemistry*; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics / Q000627:therapeutic use; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: C496789:9-fluorenylmethoxycarbonyl; D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D005449:Fluorenes; D008823:Micelles; D010455:Peptides; D016159:Tumor Suppressor Protein p53; D004317:Doxorubicin; D004247:DNA