Modulating the Oxidation Degree of Linear Polyethyleneimine for Preparation of Highly Efficient and Low-cytotoxicity Degradable Gene Delivery Carriers

Polyethyleneimine (PEI), as a widely used polymer material in the field of gene delivery, has been extensively studied for modification and shielding to reduce its cytotoxicity. However, research aimed at preparing degradable PEI is scarce. In this work, the hydrogen peroxide (H₂O₂) oxidation method was used to introduce degradable amide groups in the PEI and a series of oxidized PEI22k (oxPEI22k) with different degrees of oxidation were synthesized by regulating the dosage of H₂O₂. The relationship between the oxidation degree of oxPEI22k and the gene transfection efficiency of oxPEI22k was studied in detail, confirming that the oxPEI22k with oxidation degrees of 16.7% and 28.6% achieved improved transfection efficiency compared to unmodified PEI. These oxPEI22k also proved reduced cytotoxicity and improved degradability. Further, this strategy was extended to the synthesis of low-molecular-weight oxPEI1.8k. The oxPEI1.8k with suitable oxidation degree also achieved improved transfection efficiency and reduced cytotoxicity. In brief, this work provided high-efficiency and low-cytotoxicity degradable gene delivery carriers by regulating the oxidation degree of PEI, which was of great significance for promoting clinical applications of PEI.