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Coupling of a bifunctional peptide R13 to OTMCS-PEI copolymer as a gene vector increases transfection efficiency and tumor targeting

Authors Lv H, Zhu Q, Liu K, Zhu M, Zhao W, Mao Y, Liu K

Received 25 December 2013

Accepted for publication 21 January 2014

Published 11 March 2014 Volume 2014:9(1) Pages 1311—1322

DOI https://doi.org/10.2147/IJN.S59726

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Hui Lv,1,* Qing Zhu,1,* Kewu Liu,2 Manman Zhu,1 Wenfang Zhao,1 Yuan Mao,1 Kehai Liu1

1Department of Biopharmaceutics, College of Food Science and Technology, Shanghai Ocean University, Shanghai, People's Republic of China; 2Heilongjiang Forest By-Product and Speciality Institute, Mudanjiang, People's Republic of China

*These authors contributed equally to this work

Background: A degradable polyethylenimine (PEI) derivative coupled to a bifunctional peptide R13 was developed to solve the transfection efficiency versus cytotoxicity and tumor-targeting problems of PEI when used as a gene vector.
Methods: We crossed-linked low molecular weight PEI with N-octyl-N-quaternary chitosan (OTMCS) to synthesize a degradable PEI derivative (OTMCS-PEI), and then used a bifunctional peptide, RGDC-Tat (49–57) called R13 to modify OTMCS-PEI so as to prepare a new gene vector, OTMCS-PEI-R13. This new gene vector was characterized by various physicochemical methods. Its cytotoxicity and gene transfection efficiency were also determined both in vitro and in vivo.
Results: The vector showed controlled degradation and excellent buffering capacity. The particle size of the OTMCS-PEI-R13/DNA complexes was around 150–250 nm and the zeta potential ranged from 10 mV to 30 mV. The polymer could protect plasmid DNA from being digested by DNase I at a concentration of 23.5 U DNase I/µg DNA. Further, the polymer was resistant to dissociation induced by 50% fetal bovine serum and 400 µg/mL sodium heparin. Compared with PEI 25 kDa, the OTMCS-PEI-R13/DNA complexes showed higher transfection efficiency both in vitro and in vivo. Further, compared with OTMCS-PEI, distribution of OTMCS-PEI-R13 at tumor sites was markedly enhanced, indicating the tumor-targeting specificity of R13.
Conclusion: OTMCS-PEI-R13 could be a potential candidate as a safe and efficient gene delivery carrier for gene therapy.

Keywords: nonviral gene vector, polyethylenimine, R13, transfection efficiency, tumor-targeting

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