caa a22 4500 445313471 CHVBK 20180317142638.0 cr unu---uuuuu 170323e20110401xx s 000 0 eng 10.1007/s11095-010-0353-x doi (NATIONALLICENCE)springer-10.1007/s11095-010-0353-x In Vivo Anti-Tumor Effect of Expressing p14ARF-TAT Using a FGF2-Targeted Cationic Lipid Vector [Elektronische Daten] [Guoqin Niu, Wouter Driessen, Sean Sullivan, Jeffrey Hughes] ABSTRACT: Purpose: To develop an efficient and safe strategy to introduce a therapeutic gene into target cells in vivo for cancer therapy. The overall efficiency is based on proper selection of the delivery vector and expressed protein. Methods: A plasmid coding for a specific cytotoxic fusion peptide, p14ARF-TAT, was evaluated in a xenograft mouse tumor model. The expressed peptide consisted of three domains, a secretory signal, a membrane permeability segment and a cytotoxic fragment. Gene expression was verified in U87-MG cells by Western blot and cytotoxicity confirmed with CyQuant assay. To improve the delivery, a FGF2 targeting peptide, MQLPLATC, was incorporated into the vector, which was evaluated using a luciferase-expressing plasmid. Results: The luciferase activity in vitro was two-fold higher with the targeted formulations, and cytotoxicity was three-fold higher with expression of the p14ARF-TAT protein. A murine xenograph model of human glioma (U87-MG cells) tumors was used to address in vivo activity. FGF2-targeted lipoplexes demonstrated increased tumor volume reduction as compared to non-targeted formulations. RT-PCR and Western blot of tumor homogenizes indicated p14ARF-TAT expression in tumors along with other tissues. Conclusion: p14ARF-TAT was cytotoxic and is a promising approach when combined with an efficient targeting. Springer Science+Business Media, LLC, 2011 anti-tumor effect nationallicence cationic liposome nationallicence fibroblast growth factor (FGF2) nationallicence fusion cytotoxic gene nationallicence lipid-based gene delivery nationallicence Niu Guoqin Department of Pharmaceutics, College of Pharmacy, University of Florida, 32610, Gainesville, Florida, USA aut Driessen Wouter Department of Pharmaceutics, College of Pharmacy, University of Florida, 32610, Gainesville, Florida, USA aut Sullivan Sean Vical Incorporated, 10390 Pacific Center Court, 92121, San Diego, California, USA aut Hughes Jeffrey Department of Pharmaceutics, College of Pharmacy, University of Florida, 32610, Gainesville, Florida, USA aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/4(2011-04-01), 720-730 0724-8741 28:4<720 2011 28 11095 https://doi.org/10.1007/s11095-010-0353-x text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-010-0353-x text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Niu Guoqin Department of Pharmaceutics, College of Pharmacy, University of Florida, 32610, Gainesville, Florida, USA aut NATIONALLICENCE 700 1- Driessen Wouter Department of Pharmaceutics, College of Pharmacy, University of Florida, 32610, Gainesville, Florida, USA aut NATIONALLICENCE 700 1- Sullivan Sean Vical Incorporated, 10390 Pacific Center Court, 92121, San Diego, California, USA aut NATIONALLICENCE 700 1- Hughes Jeffrey Department of Pharmaceutics, College of Pharmacy, University of Florida, 32610, Gainesville, Florida, USA aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/4(2011-04-01), 720-730 0724-8741 28:4<720 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer