Document Detail

Efficacy and safety of dendrimer nanoparticles with coexpression of tumor necrosis factor-α and herpes simplex virus thymidine kinase in gene radiotherapy of the human uveal melanoma OCM-1 cell line.
MedLine Citation:
PMID:  24124368     Owner:  NLM     Status:  Publisher    
Human uveal melanoma is the most common primary intraocular tumor, and brachytherapy is one of the most common and effective treatment strategies. In order to find a safer and more effective way to increase the radio sensitivity of the tumor, we tried to use the dendrimer nanoparticle performing coexpression gene radiotherapy. In this study, we constructed recombinant DNA plasmids (early growth response-1 tumor necrosis factor-α [pEgr1-TNFα], pEgr1 thymidine kinase [TK], and pEgr1-TNFα-TK) according to the Egr1 promoter sequence. The sequences of human TNFα and herpes simplex virus (HSV) TK that were published by GenBank. Agarose gel electrophoresis and DNA sequencing had proven that we constructed the double-gene recombined plasmids pEgr1-TNF-TK correctly, as well as the plasmids pEgr1-TNFα and pEgr1-TK. The dendrimer nanoparticles combined with plasmid DNA as dendriplexes were verified with agarose gel electrophoresis and observed by transmission electron microscopy (TEM) and scanning electron microscopy to define size and shape. Zeta potential was measured using a Zetasizer analyzer. Optimal size and neutral zeta-potential characteristics of dendriplexes were achieved for the transfection studies. DNase I examination proved that the dendriplexes could protect plasmid DNA for at least 6 hours. The recombinant plasmids were transfected with dendrimer nanoparticles into the human choroidal melanoma OCM-1 cell line, followed by exposure to iodine-125 ((125)I) after transfection. After transfection with dendrimer nanoparticles and the irradiation of (125)I, the gene expressions of TNFα and HSV1-TK were significantly increased at the protein level by enzyme-linked immunosorbent assay and Western blot analysis in OCM-1 cells. The cellular morphology of OCM-1 cells altering was observed by TEM, and a decrease in cell proliferation was revealed in cell-growth curves. Flow cytometry of annexin V/propidium iodide double-dyeing apoptosis and caspase-3 fluorescence staining showed that this treatment method could turn transfected OCM-1 cells into apoptosis and necrosis by the effects of the gene expression. This study indicated that the dendrimer nanoparticles with coexpression of TNF-α and HSV1-TK gene therapy are effective and safe and can provide us with a novel strategy to treat human uveal melanoma in the future.
Yingchih Wang; Li Mo; Wenbin Wei; Xuehui Shi
Related Documents :
9448298 - Targeted disruption of mouse centromere protein c gene leads to mitotic disarray and ea...
15772128 - The homeodomain protein pal-1 specifies a lineage-specific regulatory network in the c....
15733658 - Mouse ovary developmental rna and protein markers from gene expression profiling.
16885538 - Naturally suppressed apoptosis prevents follicular atresia and oocyte reserve decline i...
8634708 - A gene (srpx) encoding a sushi-repeat-containing protein is deleted in patients with x-...
7533118 - Sequence of the functional human keratin k14 promoter.
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-10-02
Journal Detail:
Title:  International journal of nanomedicine     Volume:  8     ISSN:  1178-2013     ISO Abbreviation:  Int J Nanomedicine     Publication Date:  2013  
Date Detail:
Created Date:  2013-10-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101263847     Medline TA:  Int J Nanomedicine     Country:  -    
Other Details:
Languages:  ENG     Pagination:  3805-3816     Citation Subset:  -    
Beijing Tongren Eye Center, Capital Medical University, Beijing, People's Republic of China.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Targeted hyperthermia after selective embolization with ferromagnetic nanoparticles in a VX2 rabbit ...
Next Document:  Hyaluronic acid-coated bovine serum albumin nanoparticles loaded with brucine as selective nanovecto...