Trigger-responsive, fast-degradable poly(β-amino ester)s for enhanced DNA unpackaging and reduced toxicity

Area of Science:

• Polymer Chemistry
• Biomaterials Science
• Gene Therapy

Background:

• Poly(β-amino ester)s (PBAEs) are promising cationic gene delivery vectors.
• Uncontrolled DNA release and high material toxicity limit current PBAE applications.
• Slow degradation of the polyester backbone contributes to these limitations.

Purpose of the Study:

• To design and synthesize photo-responsive PBAEs with trigger-cleavable domains.
• To enhance intracellular DNA release and reduce material toxicity using UV light.
• To improve gene delivery efficiency in mammalian cells.

Main Methods:

• Synthesized photo-responsive PBAEs via polyaddition of (2-nitro-1,3-phenylene)bis(methylene) diacrylate and a bifunctional amine.
• Incorporated nitrobenzene moieties into the PBAE backbone for UV light sensitivity.
• Investigated polymer degradation, DNA release, and transfection efficiency in mammalian cell lines upon UV irradiation.

Main Results:

• The synthesized PBAEs rapidly degraded within minutes upon UV irradiation, cleaving ester linkers.
• UV-triggered degradation promoted enhanced DNA unpackaging post-transfection.
• High molecular weight PBAEs demonstrated effective gene delivery, with UV treatment significantly reducing toxicity and improving transfection rates across tested cell types.

Conclusions:

• Photo-responsive PBAEs offer a strategy for precise control over gene release and material toxicity.
• UV-triggered degradation of PBAEs addresses key challenges in non-viral gene delivery.
• This approach provides a versatile platform for developing safer and more effective gene delivery systems.