Journal
JOURNAL OF CONTROLLED RELEASE
Volume 149, Issue 3, Pages 264-272Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2010.10.032
Keywords
Gene delivery; Non-covalent association; Folate-associated lipoplexes; Serum resistance; DNA protection
Funding
- Portuguese Foundation for Science and Technology [PTDC/BIO/65627/2006, SFRH/BD/39727/2007]
- Fundação para a Ciência e a Tecnologia [SFRH/BD/39727/2007, PTDC/BIO/65627/2006] Funding Source: FCT
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The success of gene therapy depends on the efficient delivery of therapeutic genes into target cells in vitro and in vivo. Non-viral vectors, such as cationic liposome-DNA complexes (lipoplexes), have been used for numerous gene delivery applications, although their efficacy is still limited, particularly when compared to that of viral vectors. In this work, we assessed the efficacy of a new gene delivery system generated by non-covalent association of folate to lipoplexes (FA-associated lipoplexes) in two different cancer cell lines (SCC-VII and TSA cells). Association of FA with liposomes composed of DOTAP and cholesterol, and subsequent complexation with DNA greatly increased transfection efficiency above that obtained with plain lipoplexes in both cell lines. The addition of 40 mu g of FA to lipoplexes was optimal for transfection and allowed to overcome the inhibitory effect induced by the presence of serum. Notably, the biological activity of the FA-associated complexes was even significantly improved under these conditions. Transfection activity mediated by FA-associated lipoplexes was compared with that by FA-conjugated lipoplexes, and the results showed that electrostatic association of FA to the lipoplexes led to considerably higher levels of biological activity than that involving covalent coupling of FA. Moreover, FA-associated lipoplexes confer greater DNA protection than FA-conjugated lipoplexes. To our knowledge, this is the first study reporting the characterization and application of FA-associated lipoplexes in gene delivery and showing their greater efficacy than that of FA-conjugated lipoplexes. Overall, the results obtained in the present work constitute a strong indication that the developed FA-associated lipoplexes are promising candidates for in vivo gene delivery. (C) 2010 Elsevier B.V. All rights reserved.
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