Enhancing the in vivo stability of polycation gene carriers by using PEGylated hyaluronic acid as a shielding system
Jiaxue Liu, Xiao-Li Bao, Ирина А. Колесник, Boyan Jia, Zihan Yu, Caiyun Xing, Jiawen Huang, Tingting Gu, Xiaotong Shao, Alexey V. Kletskov, Andreii S. Kritchenkov, В. И. Поткин, Wenliang Li
Abstract
Abstract To increase the in vivo stability of cationic gene carriers and avoid the adverse effects of their positive charge, we synthesized a new shielding material by conjugating low molecular weight polyethylene glycol (PEG) to a hyaluronic acid (HA) core. The HA-PEG conjugate assembled with the positively charged complex, forming a protective layer through electrostatic interactions. DNA/polyetherimide/HA-PEG (DNA/PEI/HA-PEG) nanoparticles had higher stability than both DNA/polyethyleneimine (DNA/PEI) and DNA/PEI/HA complexes. Furthermore, DNA/PEI/HA-PEG nanoparticles also showed a diminished nonspecific response toward serum proteins in vivo . The in vivo transfection efficiency was also enhanced by the low cytotoxicity and the improved stability; therefore, this material might be promising for use in gene delivery applications.