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

• Published in: Biomaterials science 2019-12, Vol.8 (1), p.29-31
• Main Authors: Duan, Shanzhou, Cao, Desheng, Li, Xudong, Zhu, Huifang, Lan, Min, Tan, Zhengzhong, Song, Ziyuan, Zhu, Rongying, Yin, Lichen, Chen, Yongbing
• Format: Article
• Language: English
• ISSN: 2047-4830; 2047-4849
• DOI: 10.1039/c9bm01452g

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. Photo-degradable, branched poly(β-amino ester)s (BPAE-NB) were developed to mediate topology-assisted trans-membrane gene delivery as well as photo-strengthened intracellular gene release.