title: Peptide-Mediated Tumor Targeting by a Degradable Nano Gene Delivery Vector Based on Pluronic-Modified Polyethylenimine.
abstract: Polyethylenimine (PEI) is considered to be a promising non-viral gene delivery vector. To solve the toxicity versus efficacy and tumor-targeting challenges of PEI used as gene delivery vector, we constructed a novel non-viral vector DR5-TAT-modified Pluronic-PEI (Pluronic-PEI-DR5-TAT), which was based on the attachment of low-molecular-weight polyethylenimine (LMW-PEI) to the amphiphilic polymer Pluronic to prepare Pluronic-modified LMW-PEI (Pluronic-PEI). This was then conjugated to a multifunctional peptide containing a cell-penetrating peptide (TAT) and a synthetic peptide that would bind to DR5-a receptor that is overexpressed in cancer cells. The vector showed controlled degradation, favorable DNA condensation and protection performance. The Pluronic-PEI-DR5-TAT/DNA complexes at an N/P ratio of 15:1 were spherical nanoparticles of 122 ± 11.6 nm and a zeta potential of about 22 ± 2.8 mV. In vitro biological characterization results indicated that Pluronic-PEI-DR5-TAT/DNA complexes had a higher specificity for the DR5 receptor and were taken up more efficiently by tumor cells than normal cells, compared to complexes formed with PEI 25 kDa or Pluronic-PEI. Thus, the novel complexes showed much lower cytotoxicity to normal cells and higher gene transfection efficiency in tumor cells than that exhibited by PEI 25 kDa and Pluronic-PEI. In summary, our novel, degradable non-viral tumor-targeting vector is a promising candidate for use in gene therapy.
authors.affiliation: Department of Pharmacy, Jiaxing Maternal and Child Health Care Hospital, Affiliated Hospital of Jiaxing University, Jiaxing, People's Republic of China.
authors.forename: Zhaoyong
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Pharmaceutics, Medical College of Jiaxing University, Jiaxing, People's Republic of China.
authors.forename: Shuyu
authors.initials: S
authors.lastname: Zhan
authors.affiliation: Department of Pharmacy, The 425th Hospital of PLA, Sanya, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Fan
authors.affiliation: Department of Pharmaceutics, Shanghai First People's Hospital, Shanghai Jiaotong University, Shanghai, People's Republic of China.
authors.forename: Xueying
authors.initials: X
authors.lastname: Ding
authors.affiliation: Department of Pharmaceutics, Shanghai First People's Hospital, Shanghai Jiaotong University, Shanghai, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Pharmacy, Shanghai Pulmonary Hospital, Shanghai, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutics, Medical College of Jiaxing University, Jiaxing, People's Republic of China.
authors.forename: Yinghua
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Department of Pharmaceutics, Medical College of Jiaxing University, Jiaxing, People's Republic of China.
authors.forename: Yueyan
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Pharmaceutics, Medical College of Jiaxing University, Jiaxing, People's Republic of China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Pharmaceutics, Medical College of Jiaxing University, Jiaxing, People's Republic of China.
authors.forename: Rubing
authors.initials: R
authors.lastname: Chen
authors.affiliation: Department of Pharmaceutics, Medical College of Jiaxing University, Jiaxing, People's Republic of China.
authors.forename: Mingjuan
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Pharmaceutics, Medical College of Jiaxing University, Jiaxing, People's Republic of China.
authors.forename: Ningyin
authors.initials: N
authors.lastname: Xu
authors.affiliation: Department of Pharmaceutics, Medical College of Jiaxing University, Jiaxing, People's Republic of China. zhengyongxia@163.com.
authors.forename: Yongxia
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Pharmaceutics, Medical College of Jiaxing University, Jiaxing, People's Republic of China. lena_310@163.com.
authors.forename: Baoyue
authors.initials: B
authors.lastname: Ding
keywords: Cytotoxicity; DR5-TAT peptide; Pluronic-PEI; Transfection efficiency; Tumor-targeting gene delivery system