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Hydrophobic poly (amino acid) modified PEI mediated delivery of rev-casp-3 for cancer therapy

Author:
Fu, Chunling, Lin, Lin, Shi, Hengliang, Zheng, Daxue, Wang, Wei, Gao, Shiqian, Zhao, Yifei, Tian, Huayu, Zhu, Xiaojuan, Chen, Xuesi
Source:
Biomaterials 2012 v.33 no.18 pp. 4589-4596
ISSN:
0142-9612
Subject:
adverse effects, amino acids, apoptosis, biocompatibility, cytotoxicity, drugs, genes, growth retardation, hydrophobicity, mice, models, neoplasms, plasmids, polymers, small interfering RNA, therapeutics, transfection
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.
Agid:
904230