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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.
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Liu et al. (2022) studied this question.
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