Back to Journals » International Journal of Nanomedicine » Volume 7

A pH-sensitive multifunctional gene carrier assembled via layer-by-layer technique for efficient gene delivery

Authors Li, Liu D, Miao, Liu, Sun, Liu Y, Zhang N

Received 7 October 2011

Accepted for publication 24 November 2011

Published 21 February 2012 Volume 2012:7 Pages 925—939

DOI https://doi.org/10.2147/IJN.S26955

Review by Single-blind

Peer reviewer comments 3

Peng Li, Donghua Liu, Lei Miao, Chunxi Liu, Xiaoli Sun, Yongjun Liu, Na Zhang

School of Pharmaceutical Science, Shandong University, Jinan, Shandong, People’s Republic of China

Background: The success of gene therapy asks for the development of multifunctional vectors that could overcome various gene delivery barriers, such as the cell membrane, endosomal membrane, and nuclear membrane. Layer-by-layer technique is an efficient method with easy operation which can be used for the assembly of multifunctional gene carriers. This work describes a pH-sensitive multifunctional gene vector that offered long circulation property but avoided the inhibition of tumor cellular uptake of gene carriers associated with the use of polyethylene glycol.
Methods: Deoxyribonucleic acid (DNA) was firstly condensed with protamine into a cationic core which was used as assembly template. Then, additional layers of anionic DNA, cationic liposomes, and o-carboxymethyl-chitosan (CMCS) were alternately adsorbed onto the template via layer-by-layer technique and finally the multifunctional vector called CMCS-cationic liposome-coated DNA/protamine/DNA complexes (CLDPD) was constructed. For in vitro test, the cytotoxicity and transfection investigation was carried out on HepG2 cell line. For in vivo evaluation, CMCS-CLDPD was intratumorally injected into tumor-bearing mice and the tumor cells were isolated for fluorescence determination of transfection efficiency.
Results: CMCS-CLDPD had ellipsoidal shapes and showed “core-shell” structure which showed stabilization property in serum and effective protection of DNA from nuclease degradation. In vitro and in vivo transfection results demonstrated that CMCS-CLDPD had pH-sensitivity and the outermost layer of CMCS fell off in the tumor tissue, which could not only protect CMCS-CLDPD from serum interaction but also enhance gene transfection efficiency.
Conclusion: These results demonstrated that multifunctional CMCS-CLDPD had pH-sensitivity, which may provide a new approach for the antitumor gene delivery.

Keywords: layer-by-layer, multifunctional nanovector, pH-sensitivity, gene delivery

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]