| Autor: |
Li J; Center for Drug Delivery and Nanomedicine, Department of Pharmaceutical Sciences, University of Nebraska Medical Center , Omaha, Nebraska 68198, United States., Lepadatu AM, Zhu Y, Ciobanu M, Wang Y, Asaftei SC, Oupický D |
| Jazyk: |
angličtina |
| Zdroj: |
Bioconjugate chemistry [Bioconjug Chem] 2014 May 21; Vol. 25 (5), pp. 907-17. Date of Electronic Publication: 2014 May 12. |
| DOI: |
10.1021/bc500191q |
| Abstrakt: |
Chemokine receptors and their ligands play a central role in cancer metastasis, inflammatory disorders, and viral infections. Viologen dendrimers (VGD) emerged recently as a promising class of synthetic polycationic ligands for chemokine receptor CXCR4. The objective of this study was to evaluate the potential of VGD as novel dual-function polycations capable of simultaneous CXCR4 antagonism and gene delivery. As part of our systematic studies, we have synthesized a library of VGD with differences in molecular architecture, number of positive charges, and type of capping group. The ability of VGD to condense DNA was evaluated, and physicochemical and biological properties of the resulting polyplexes were studied. We have evaluated the effect of VGD surface charge, size, capping group, and molecular architecture on physicochemical properties of polyplexes, transfection efficiency, CXCR4 antagonism, and cytotoxicity in human epithelial osteosarcoma (U2OS) and in human liver hepatocellular carcinoma (HepG2) cells. We found that properties and behavior of the polyplexes are most dependent on the number of positive charges and molecular weight of VGD and to a lesser extent on the type of a capping group. Using TNFα plasmid, we have demonstrated that VGD prevents CXCR4-mediated cancer cell invasion and facilitates TNFα-mediated cancer cell killing. Such dual-function carriers have potential to enhance the overall therapeutic outcomes of cancer gene therapy. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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