PEG-PCL-DEX polymersome-protamine vector as an efficient gene delivery system via PEG-guided self-assembly

Area of Science:

• Biotechnology
• Nanomedicine
• Gene Delivery

Background:

• Nonviral gene delivery systems are crucial for therapeutic applications.
• Developing efficient and safe carriers for nucleic acids remains a challenge.

Purpose of the Study:

• To develop a novel nonviral carrier system using triblock copolymer PEG-PCL-DEX (PPD) and protamine for nucleic acid delivery.
• To evaluate the efficacy and safety of this system for gene silencing in liver cells.

Main Methods:

• Polymersomes were formed via self-assembly of PEG-PCL-DEX.
• siRNA was condensed by protamine and encapsulated into PPD polymersomes.
• Nanoparticle characterization included size, ζ-potential, cellular uptake, and gene silencing efficacy.

Main Results:

• PPD-protamine siRNA nanoparticles were formed with a size of 145.2 ± 8.02 nm and reduced ζ-potential.
• Effective cellular uptake and significant GL3 gene expression reduction (61.73 ± 6.25%) were observed in SMMC-7721 cells.
• Negligible cytotoxicity and preferential accumulation in the liver were noted in biodistribution studies.

Conclusions:

• The PPD-protamine carrier system demonstrates potential for effective siRNA delivery.
• This system shows promise as a gene delivery strategy for treating liver-related diseases.