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Self-assembled supramolecular nano vesicles for safe and highly efficient gene delivery to solid tumors

Authors Li W, Li H, Li J, Wang H, Zhao H, Zhang L, Xia Y, Ye Z, Gao J, Dai J, Wang H, Guo Y

Received 6 June 2012

Accepted for publication 13 July 2012

Published 22 August 2012 Volume 2012:7 Pages 4661—4677

DOI https://doi.org/10.2147/IJN.S34675

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Wei Li,1,2,* Huafei Li,1,* Jinfeng Li,1,* Huajing Wang,1,* He Zhao,1 Li Zhang,1 Yu Xia,1 Zengwei Ye,1 Jie Gao,1,2 Jianxin Dai,1–3 Hao Wang,1–3 Yajun Guo1–3

1
International Joint Cancer Institute, The Second Military Medical University, Shanghai, 2National Engineering Research Center for Antibody Medicine, State Key Laboratory of Antibody Medicine and Targeting Therapy and Shanghai Key Laboratory of Cell Engineering, Shanghai, 3PLA General Hospital Cancer Center, PLA Graduate School of Medicine, Beijing, People's Republic of China

*These authors contributed equally to this work

Abstract: The main obstacles for cationic polyplexes in gene delivery are in vivo instability and low solid-tumor accumulation. Safe vectors with high transfection efficiency and in vivo tumor accumulation are therefore highly desirable. In this study, the amphiphilic block copolymer poly(n-butyl methacrylate)-b-poly(N-acryloylmorpholine) was synthesized by reversible addition–fragmentation chain-transfer (RAFT) radical polymerization. The corresponding well-defined vesicles with narrow size distribution were tailored by finely regulating the packing parameter (β) of copolymer (1/2 < β < 1). Compared with traditional "gold-standard" polycation (polyethylenimine, 25 kDa), plasmid DNA condensing efficiency, DNase I degradation protection, and cellular uptake were improved by the supramolecular nano vesicles. In addition, the plasmid DNA transferring efficiency in 10% fetal bovine serum medium was enlarged five times to that of polyethylenimine in renal tubular epithelial and human hepatocellular carcinoma cell lines. This improved in vitro transfection was mainly attributed to the densely packed bilayer. This stealth polyplex showed high serum stability via entropic repulsion, which further protected the polyplex from being destroyed during sterilization. As indicated by the IVIS® Lumina II Imaging System (Caliper Life Sciences, Hopkinton, MA) 24 hours post-intravenous administration, intra-tumor accumulation of the stealth polyplex was clearly promoted. This study successfully circumvented the traditional dilemma of efficient gene transfection at a high nitrogen-from-polyethylenimine to phosphate-from-DNA ratio that is accompanied with site cytotoxicity and low stability. As such, these simply tailored non-cytotoxic nano vesicles show significant potential for use in practical gene therapy.

Keywords: block copolymer, nano vesicle, gene transfection, serum stability, intra-tumor accumulation

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