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Squalene/polyethylenimine based non-viral vectors: synthesis and use in systems for sustained gene release

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Abstract

The design of new non-viral gene vectors and their integration into a biomaterial scaffold are intensively explored nowadays, aimed at developing more efficient gene delivery systems capable of clinical translation. Herein, a series of squalene/branched polyethylenimine (Sq/BPEI) based conjugates were synthesized and their potential in gene delivery, as such or included in a three-dimensional hybrid scaffold (atelocollagen-glycosaminoglycan-polycaprolactone/nano-hydroxyapatite), was investigated. The developed materials were characterized through spectral (1H-NMR, 13C-NMR, FT-IR) and optical (STEM) techniques. The extent and duration of gene expression for the developed systems were monitored using luciferase assays and fluorescence microscopy. All the investigated systems exhibited a high transfection efficiency without or with moderate cytotoxic side effects (MTS assay data). The best results were obtained with the guanidinylated compound Sq-BPEI-G for both simple and combined polyplex/matrix systems. The polyplex delivery from the hybrid matrix was assessed through kinetic studies using a labeled Sq/BPEI conjugate. For the polyplex (Sq/BPEI – DNA plasmid)/3D matrix system, the expression of the delivered plasmids was observed over a 26 day- period. The reported preliminary data recommend the studied biomaterials as possible candidates for the development of a new gene-activated matrix (GAM) platform.

Graphical abstract: Squalene/polyethylenimine based non-viral vectors: synthesis and use in systems for sustained gene release

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Publication details

The article was received on 10 Oct 2017, accepted on 08 Jan 2018 and first published on 25 Jan 2018


Article type: Paper
DOI: 10.1039/C7PY01720K
Citation: Polym. Chem., 2018, Advance Article
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    Squalene/polyethylenimine based non-viral vectors: synthesis and use in systems for sustained gene release

    G. David, L. Clima, M. Calin, C. A. Constantinescu, M. Balan-Porcarasu, C. M. Uritu and B. C. Simionescu, Polym. Chem., 2018, Advance Article , DOI: 10.1039/C7PY01720K

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