N,N,N-trimethylchitosan modified with well defined multifunctional polymer modules used as pDNA delivery vector

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Gene Therapy

Background:

• Chitosan is a promising biomaterial for gene delivery but requires modification to enhance its properties.
• Non-viral gene carriers offer a safer alternative to viral vectors but often face challenges in efficiency and solubility.

Purpose of the Study:

• To develop a novel, non-viral gene carrier based on N,N,N-trimethylchitosan (TMC).
• To improve the water solubility, pDNA packaging ability, and gene transfection efficiency of chitosan-based materials.

Main Methods:

• Synthesis of a well-defined copolymer P(PEGMA-co-DMAEMA) via RAFT polymerization.
• Grafting of allyl groups onto TMC to create Allyl-TMC.
• Sequential grafting of P(PEGMA-co-DMAEMA) and folate onto Allyl-TMC to yield TMC-g-P(PEGMA-co-DMAEMA)-FA.

Main Results:

• The fabricated TMC-g-P(PEGMA-co-DMAEMA)-FA exhibited superior water solubility and pDNA packaging compared to pristine chitosan.
• Gene delivery efficiency was evaluated using different molecular weights of chitosan.
• The 20k-TMC-g-P(PEGMA-co-DMAEMA)-FA/pDNA complex showed the highest transfection efficiency in 293 T cells at a weight ratio of 20.

Conclusions:

• A novel and efficient chitosan-based gene carrier was successfully fabricated.
• The modified chitosan demonstrates potential for improved gene delivery applications.
• This study presents a new strategy for modifying chitosan for enhanced gene carrier functionality.