Photosensitive Peptidomimetic for Light-Controlled, Reversible DNA Compaction.

Area of Science:

• Biomaterials Science
• Molecular Biology
• Nanotechnology

Background:

• Nonviral gene delivery seeks efficient DNA compaction using light-sensitive agents.
• Previous agents lacked biocompatibility or effective light-induced control.
• Bridging artificial light-switchable and biocompatible agents remained a challenge.

Purpose of the Study:

• To investigate light-induced DNA compaction and decompaction using a novel multivalent cationic peptidomimetic molecule with a photosensitive Azo-group (Azo-PM).
• To explore the potential of Azo-PM as a biocompatible and photoswitchable agent for gene delivery.

Main Methods:

• Synthesis of Azo-PM via solid-phase procedure, incorporating an azobenzene unit onto an oligo(amidoamine) backbone.
• Characterization of DNA compaction/decompaction using dynamic light scattering and Atomic Force Microscopy (AFM).
• Molecular dynamics simulations to elucidate Azo-PM-DNA interactions.

Main Results:

• Azo-PM induces reversible DNA compaction/decompaction upon specific light illumination through photoisomerization of the Azo-group.
• The peptidomimetic backbone of Azo-PM dominates DNA interaction, distinct from surfactant-based agents.
• Molecular dynamics simulations support Azo-PM acting as a multivalent counterion with fine-tuned Azo-moiety influence.

Conclusions:

• Azo-PM demonstrates effective light-controlled DNA compaction and decompaction.
• The peptidomimetic nature suggests lower toxicity compared to photosensitive surfactants.
• Azo-PM represents a potential foundation for designing advanced, photoswitchable, and biocompatible gene delivery vectors.