Dextranation of Bioreducible Cationic Polyamide for Systemic Gene Delivery

Issue title: Frontiers in Biomedical Engineering and Biotechnology – Proceedings of the 2nd International Conference on Biomedical Engineering and Biotechnology, 11–13 October 2013, Wuhan, China

Article type: Research Article

Authors: Lin, Chao^{; ;} | Song, Yanyan^{; ;} | Lou, Bo^; | Zhao, Peng^;

Affiliations: The Institute for Biomedical Engineering and Nanoscience, Tongji University School of Medicine, Tongji University, Shanghai, 200092, P.R. China | School of Life Sciences and Technology, Tongji University, Shanghai, 200092, P.R. China

Note: [] Corresponding author. E-mail: chaolin@tongji.edu.cn (CL), zhaopeng.shanghai@gmail.com (PZ)

Note: [] The authors contribute equally as co-first author.

Note: [] The authors contribute equally as co-first author.

Note: [] Corresponding author. E-mail: chaolin@tongji.edu.cn (CL), zhaopeng.shanghai@gmail.com (PZ)

Abstract: A dextranated, bioreducible cationic polyamide was designed and employed for non-viral gene delivery in vitro and in vivo. Initially, a new bioreducible cationic polyamide with p-nitrophenyl ester terminal group (denoted as SSBAP) was synthesized by polycondensation reaction of an excess amount of bis-(p-nitrophenyl)-3, 3'-dithiodipropanoate and 1, 4-bis(3-aminopropyl)piperazine. The SSBAP was then chemically conjugated with 5kDa amino-terminated dextran to yield dextran-SSBPA-dextran triblock copolymer (denoted as Dex-SSBAP-Dex). This copolymer was capable of binding genes to form nanoscale polyplexes with a near-neutral surface charge. Moreover, a sufficient gene release from the polyplexes in response to an intracellular reducing environment was observed. In vitro transfection against MCF-7 and SKOV-3 cells showed that Dex-SSBAP-Dex copolymer effectively transfected the cells with comparable efficiency to that of 25kDa branched or linear polyethylenimine as positive controls. Besides, intravenous administration of the copolymer-based polyplexes in nude mice afforded detectable gene expression largely in the lung. Importantly, the copolymer revealed low cytotoxicity in vitro, as determined by AlamarBlue assay, and caused no death of the mice. Dextranated, bioreducible cationic polyamide holds high potential as a non-viral vector for gene delivery.

Keywords: Dextran, disulfide, gene delivery, transfection, in vivo

DOI: 10.3233/BME-130855

Journal: Bio-Medical Materials and Engineering, vol. 24, no. 1, pp. 673-682, 2014