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New tumor-targeted nanosized delivery carrier for oligonucleotides: characteristics in vitro and in vivo

Authors Zhou, Jia, Li H, Wang, Zhang H, A Y, Zhang

Published 22 July 2011 Volume 2011:6 Pages 1527—1534


Review by Single-blind

Peer reviewer comments 3

Tianyang Zhou1,2, Xin Jia1, Huixiang Li3, Jin Wang3, Hongling Zhang1,2, Youmei A1,2, Zhenzhong Zhang1,2
School of Pharmaceutical Sciences, 2Nanotechnology Research Center for Drugs, 3Department of Pathology, Medical School of Zhengzhou University, Zhengzhou, People’s Republic of China

Background: The purpose of this study was to investigate the in vitro and in vivo characteristics of a new tumor-targeted nanosized delivery carrier for antisense oligonucleotide (ASON).
Methods: Polyethylenimine (PEI) was used to condense ASON to form nanosized complexes (PEI/ASON), which were then modified using asparagine-glycine-arginine (NGR) peptide to obtain a tumor-targeted nanosized delivery carrier (NGR/PEI/ASON). The conditions required to form PEI/ASON were investigated.
Results: A linear correlation between the natural logarithm of the N/P ratio (PEI to ASON) and the zeta potential of the PEI/ASON complexes was found, ranging from 1.5 to 5.0. The pH of the solution strongly influenced the zeta potential of the PEI/ASON complexes. PEI/ASON and NGR/PEI/ASON were stable in RPMI-1640 culture medium in the presence of Dextran 70. Incorporation of ASON into PEI/ASON and NGR/PEI/ASON complexes prevented degradation of ASON by DNase I.
Conclusion: Both ASON/PEI and NGR/PEI/ASON complexes enhanced the uptake of ASON by EC9706 cells in vitro. In vivo, NGR/PEI/ASON complexes had the ability to target tumor tissues effectively.

Keywords: nanosized delivery system, squamous cell carcinoma, antisense oligonucleotide

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