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A novel potential biocompatible hyperbranched polyspermine for efficient lung cancer gene therapy

Cited 17 time in Web of Science Cited 18 time in Scopus
Authors
Xie, Rong-Lin; Jang, Yoon-jeong; Xing, Lei; Zhang, Bing-Feng; Wang, Feng-Zhen; Cui, Peng-Fei; Cho, Myung-Haing; Jiang, Hu-Lin
Issue Date
2015-01
Citation
International Journal of Pharmaceutics, Vol.478 No.1, pp.19-30
Keywords
Citric acidHyperbranched polyspermineBiocompatibilityLung cancerAerosol delivery
Abstract
The clinical successful application of gene therapy critically depends upon the development of non-toxic and efficient delivery system. Although polycationic non-viral vectors hold great promise in nanomedicine, the exploring of application in clinics still remains a big challenge. To develop a non-toxic and efficient non-viral gene delivery system, two kinds of endogenous substance, citric acid (CA) and spermine (SPE), were used to prepare a new low charge density hyperbranched polyspermine (HPSPE) by one-pot polymerization. The biocompatibility evaluated by hemolytic activity and red blood cell (RBC) aggregation indicated that HPSPE was highly biocompatible without causing hemolysis and RBC aggregation compared with PEI as well as SPE. The MTS assay also demonstrated that the cell viability of HPSPE was above 90% even at 200 mu g/mL at different time (24 and 72 h), which much higher than PEI 25 K. Besides, HPSPE showed high transfection efficiency without any toxic effect after aerosol delivery to the mice. Moreover, aerosol delivery of HPSPE/Aktl shRNA significantly reduced tumor size and numbers and efficiently suppressed lung tumorigenesis ultimately in K-ras(LA1) lung cancer model mice. These results suggest that low charge density as well as endogenous substance skeleton endow HPSPE with great potential for toxicity-free and efficient gene therapy. (C) 2014 Elsevier B.V. All rights reserved.
ISSN
0378-5173
URI
https://hdl.handle.net/10371/172406
DOI
https://doi.org/10.1016/j.ijpharm.2014.11.014
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College of Veterinary Medicine (수의과대학)Dept. of Veterinary Medicine (수의학과)Journal Papers (저널논문_수의학과)
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