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Self-assembled core-shell-corona multifunctional non-viral vector with AIE property for efficient hepatocytes targeting gene delivery

Abstract

With the aim to develop novel multifunctional gene delivery system that may overcome the common barriers in gene transfection, two amphiphilic molecules with tetraphenyl ethylene (TPE) as hydrophobic moiety and linear PEI-galactose as hydrophilic part were elaborately designed and synthesized. The molecules could self-assemble to form micelles and exhibit aggregation-induced emission (AIE) property which may be used for cell imaging. Several assays revealed that the disulfide bond in TSPG may facilitate the vector decomposition and DNA release, resulting in higher transfection efficiency and lower cytotoxicity than its counterpart TCPG and PEI 25 kDa. These vectors showed excellent serum tolerance, and even higher efficiency could be obtained in the transfection with the presence of serum. Moreover, the transfection in different cell lines showed that TSPG complex could induce higher gene expression in asialoglycoprotein receptor-riched HepG2 cells than HeLa cells, which lacks such receptor. Galactose competition assay also demonstrated that the galactose moiety could afford the vector with targeting ability toward hepatoma cells. Cellular uptake inhibition assay indicated that the DNA complex entered the cell mainly via caveolae-mediated endocytosis. Results showed that TSPG may serve as promising reagent for simultaneous gene transfection and imaging with good biocompatibility and cell targeting ability.

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Publication details

The article was received on 06 Sep 2017, accepted on 30 Oct 2017 and first published on 10 Nov 2017


Article type: Paper
DOI: 10.1039/C7PY01520H
Citation: Polym. Chem., 2017, Accepted Manuscript
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    Self-assembled core-shell-corona multifunctional non-viral vector with AIE property for efficient hepatocytes targeting gene delivery

    X. Yu, B. Wang, P. Chen, J. Zhang, X. Chen, Y. Liu, Z. Huang, Q. Yu, J. Zhang, W. Zhang and X. Wei, Polym. Chem., 2017, Accepted Manuscript , DOI: 10.1039/C7PY01520H

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