title: Hydrophobic poly (amino acid) modified PEI mediated delivery of rev-casp-3 for cancer therapy.
abstract: Recent studies in amphiphilic cationic polymers have demonstrated their potential as gene carriers with high transfection efficiency and low cytotoxicity in the in vitro settings to deliver drug, siRNA and plasmid DNA. Yet their safety and efficacy in vivo remain to be a challenge, and require further investigation. In our previous work, PP80 was synthesized as a novel amphiphilic cationic polymer by grafting hydrophobic polyphenylalanine segment on PEI, which displayed higher transfection efficiency than PEI in a number of cell lines in vitro. Here, we reported the favorable biocompatibility displayed by PP80/pDNA complex both in vitro and in vivo. Furthermore, when therapeutic gene rev-casp-3 was conjugated to PP80 and administered intratumorally to a HeLa xenograft model, significant tumor apoptosis was induced with concurrent tumor growth inhibition, indicating that PP80 mediated expression of rev-casp-3 gene in solid tumors with not detectable side effects on the tumor-bearing mice. These data demonstrated that PP80 warrants further investigation as a promising cancer gene delivery vehicle.
authors.affiliation: Key Laboratory of Molecular Epigenetics of Ministry of Education, Institute of Cytology and Genetics, Northeast Normal University, Changchun, China.
authors.forename: Chunling
authors.initials: C
authors.lastname: Fu
authors.forename: Lin
authors.initials: L
authors.lastname: Lin
authors.forename: Hengliang
authors.initials: H
authors.lastname: Shi
authors.forename: Daxue
authors.initials: D
authors.lastname: Zheng
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Shiqian
authors.initials: S
authors.lastname: Gao
authors.forename: Yifei
authors.initials: Y
authors.lastname: Zhao
authors.forename: Huayu
authors.initials: H
authors.lastname: Tian
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Zhu
authors.forename: Xuesi
authors.initials: X
authors.lastname: Chen
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D000818:Animals; D015153:Blotting, Western; D053148:Caspase 3 / Q000235:genetics* / Q000502:physiology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D024202:Electrophoretic Mobility Shift Assay; D004912:Erythrocytes / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007371:Interferon-gamma / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010957:Plasmids; D011094:Polyethyleneimine / Q000737:chemistry*; D011108:Polymers / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry*; D011817:Rabbits; D002583:Uterine Cervical Neoplasms / Q000097:blood / Q000628:therapy; D023041:Xenograft Model Antitumor Assays
chemical_list: D000596:Amino Acids; D011108:Polymers; D007371:Interferon-gamma; D011094:Polyethyleneimine; D053148:Caspase 3