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RESEARCH ARTICLE
Contents Vol 69(3)

Novel Disulfide-Containing Poly(β-amino ester)-Functionalised Magnetic Nanoparticles for Efficient Gene Delivery

Yucheng Liu A C , Shufeng Li B C , Liandong Feng A , Hao Yu A , Xiaoliang Qi A , Wei Wei A , Junjian Li A and Wei Dong A D
+ Author Affiliations
- Author Affiliations

A Center for Molecular Metabolism, Nanjing University of Science and Technology, Nanjing 210094, China.

B Key Laboratory of Developmental Genes and Human Disease in Ministry of Education, Department of Biochemistry and Molecular Biology, Medical School of Southeast University, Nanjing 210009, China.

C These authors contributed equally to this work.

D Corresponding author. Email: weidong@njust.edu.cn

Australian Journal of Chemistry 69(3) 349-356 https://doi.org/10.1071/CH15293
Submitted: 19 May 2015  Accepted: 14 August 2015   Published: 3 September 2015

Abstract

Poly(β-amino ester)s (PBAEs) have been proved to effectively transfer DNA to various cell types. However, PBAEs with high molecular weights also show considerable toxicities, partly resulting from inadequate degradation of their polyester backbone. In this study, we created novel poly(β-amino ester)s (SF-1, 2, 3, and 4; notation SFs refers to all the four polymers) which were characterised by the cleavable disulfide bonds. Moreover, a new technique, termed magnetofection that uses magnetic nanoparticles to enhance gene expression, has recently been well developed. The negatively charged magnetic nanoparticles (MNPs) with good biocompatibility in vitro were prepared here to subsequently combine with SFs and DNA via electrostatic interaction, leading to the formation of the magnetic gene complexes MNP/SFs/DNA. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays and transfection experiments were performed in A549 cells to investigate all the resulting complexes. Studies indicated that the synthesised PBAEs exhibited good biodegradation and regulated release of DNA as a result of the reductive cleavage of the disulfide bonds, giving higher transfection efficiency along with much lower cytotoxicity compared with commercially available transfection agent polyethylenimine (Mw 25 kDa). Furthermore, when MNP was involved at a MNP/DNA weight ratio of 0.5, the magnetic gene complexes MNP/SFs/DNA showed enhanced levels of gene expression while maintaining low cytotoxicity.


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