A multifunctional polymeric gene delivery system for circumventing biological barriers

Area of Science:

• Biomaterials Science
• Nanotechnology
• Gene Therapy

Background:

• Gene delivery faces challenges with endo/lysosomal entrapment and inefficient DNA release.
• Existing gene delivery systems often lack stimuli-responsive mechanisms for controlled payload release.

Purpose of the Study:

• To develop a novel tandem tri-copolymeric material for overcoming gene delivery obstacles.
• To create a light-responsive nanoscaled delivery system for enhanced gene expression.

Main Methods:

• Formulation of a tri-copolymer with β-cyclodextrin (PG), quaternary amine (BP), and hydrophobic (PDM) segments for DNA complexation.
• Integration of a light-stimulated ROS-producing component (TPE) within cyclodextrin cavities for endo/lysosomal escape.
• Utilizing light irradiation to trigger ROS production, disrupt endo/lysosomes, and induce charge conversion for DNA release.

Main Results:

• The formulated polyplex demonstrated improved complex stability through hydrophobic interactions.
• Light irradiation successfully triggered TPE to produce ROS, leading to endo/lysosomal membrane disruption.
• Charge conversion of BP and PDM's pH-responsive transformation facilitated polyplex dissociation and DNA release.

Conclusions:

• The synthesized tandem tri-copolymer effectively circumvents endo/lysosomal entrapment for gene delivery.
• The material exhibits excellent gene expression activity, responding to light and pH stimuli.
• This system offers a facile and stimuli-responsive approach for active gene expression.