Jump to main content
Jump to site search


Topology-assisted, photo-strengthened DNA/siRNA delivery mediated by branched poly(β-amino ester)s via synchronized intracellular kinetics

Author affiliations

Abstract

The performance of non-viral gene delivery vehicles, especially cationic polymers, is often challenged by the multiple cellular barriers that pose inconsistent requirements for material properties. A most pronounced inconsistency is exemplified by the molecular weight (MW)-related transfection efficiency and cytotoxicity. In this study, we report the development of photo-degradable, branched poly(β-amino ester)s (BPAE-NB) to realize efficient and photo-controlled DNA and siRNA delivery. BPAE-NB possessing built-in light-responsive 2-nitrobenzene moieties in the polymer backbone was synthesized via the A2 (amine) + B3 (triacrylate) + C2 (diacrylate) polycondensation reaction from 4-amino-1-butanol (A2), trimethylolpropane triacrylate (B3), and (2-nitro-1,3-phenylene)bis(methylene) diacrylate (NPBMDA, C2). The highly branched BPAE-NB with the multivalent arrangement of cationic groups provides stronger nucleic acid binding capacity than its linear analogue LPAE-NB, and thus features stronger trans-membrane gene delivery capabilities and higher transfection efficiencies. Upon UV light irradiation, the backbone of BPAE-NB can quickly degrade into low-MW fragments as a consequence of the cleavage of the light-responsive 2-nitrobenzene, thus promoting intracellular gene release and diminishing the toxicity of materials at the post-transfection state. As such, in multiple mammalian cells, BPAE-NB exhibited remarkably higher DNA/siRNA transfection efficiency yet lower cytotoxicity than its non-responsive analogue BPAE-CC upon light irradiation, notably outperforming commercial reagents PEI 25k and Lipofectamine 2000. This study therefore provides an effective topology- and photo-controlled approach to precisely manipulate the transfection efficiency and toxicity of polycationic gene vectors, and may also provide promising additions to the existing non-viral gene delivery vectors.

Graphical abstract: Topology-assisted, photo-strengthened DNA/siRNA delivery mediated by branched poly(β-amino ester)s via synchronized intracellular kinetics

Back to tab navigation

Supplementary files

Publication details

The article was received on 09 Sep 2019, accepted on 27 Sep 2019 and first published on 04 Oct 2019


Article type: Paper
DOI: 10.1039/C9BM01452G
Biomater. Sci., 2019, Advance Article

  •   Request permissions

    Topology-assisted, photo-strengthened DNA/siRNA delivery mediated by branched poly(β-amino ester)s via synchronized intracellular kinetics

    S. Duan, D. Cao, X. Li, H. Zhu, M. Lan, Z. Tan, Z. Song, R. Zhu, L. Yin and Y. Chen, Biomater. Sci., 2019, Advance Article , DOI: 10.1039/C9BM01452G

Search articles by author

Spotlight

Advertisements