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

Authors Zhou T, Jia X, Li H, Wang J, Zhang H, A Y, Zhang ZZ

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

DOI https://doi.org/10.2147/IJN.S15239

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
1
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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