Three-layered polyplex micelle as a multifunctional nanocarrier platform for light-induced systemic gene transfer

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Gene Therapy

Background:

• Light-responsive nanocarriers show promise for targeted therapy.
• Systemic light-selective gene transfer remains a significant challenge.

Purpose of the Study:

• To develop systemic light-responsive nanocarriers for efficient gene delivery.
• To overcome limitations in current systemic gene transfer methods.

Main Methods:

• Sequential self-assembly of triblock copolymer, DNA, and dendrimeric photosensitizer into three-layered polyplex micelles.
• Utilizing a shielding outer layer to prevent blood interactions and a photosensitizer layer for light-triggered release.
• Demonstrating multistep delivery for cytoplasmic translocation and nuclear DNA delivery.

Main Results:

• Polyplex micelles exhibited >100-fold photoenhanced gene expression in vitro.
• Achieved light-induced in vivo gene transfer in solid tumors after systemic administration.
• The three-layered structure facilitated targeted delivery and endosomal escape.

Conclusions:

• The developed nanocarriers offer a promising platform for systemic light-controlled gene delivery.
• This approach enhances gene expression and enables precise therapeutic interventions in solid tumors.
• The nanocarrier design overcomes key hurdles in systemic gene therapy applications.