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

A novel non-viral gene carrier based on N , N , N -trimethylchitosan (TMC) has been fabricated. First, well-defined copolymer P (PEGMA- co -DMAEMA) was synthesized through reversible addition fragmentation chain transfer (RAFT) polymerization of poly(ethylene glycol) methyl ether methacrylate (PEGMA) and N , N -(2-dimethylamino)ethyl methacrylamide (DMAEMA). Then allyl group grafting N , N , N -trimethylchitosan (Allyl-TMC) was synthesized via the reaction between allyl bromide and hydroxyl of TMC. Finally, P (PEGMA- co -DMAEMA) and folate were ordinally grafted onto Allyl-TMC to obtain TMC- g - P (PEGMA- co -DMAEMA)-FA. In comparison with pristine chitosan, TMC- g - P (PEGMA- co -DMAEMA)-FA has achieved both better water solubility and stronger pDNA packaging ability, which can contribute to improving gene transfection. Gene delivery efficiency of a series of TMC based functional polymers with different chitosan molecular weights has been tested. The results show that 20k-TMC- g - P (PEGMA- co -DMAEMA)-FA/pDNA complex at the weight ratio of 20 achieve the highest transfection efficiency in 293 T cells. This work presents a new strategy to modify chitosan efficiently as gene carrier material.