A Facile Strategy to Prepare Hyperbranched Hydroxyl-Rich Polycations for Effective Gene Therapy

Area of Science:

• Biomaterials Science
• Gene Therapy
• Polymer Chemistry

Background:

• Effective nonviral gene carriers are crucial for gene therapy, demanding low toxicity and high transfection efficiency.
• Existing carriers like branched polyethylenimine (PEI) have limitations in toxicity and efficiency.

Purpose of the Study:

• To develop a facile strategy for preparing hyperbranched hydroxyl-rich polycations (TE) for gene delivery.
• To evaluate the DNA condensation, protein absorption, biocompatibility, transfection efficiency, and in vivo therapeutic potential of TE.

Main Methods:

• A one-pot ring-opening reaction between ethylenediamine (ED) and 1,3,5-triglycidyl isocyanurate (TGIC) was used to synthesize TE.
• Hyperbranched TEs of varying molecular weights were characterized for their gene delivery properties.
• In vitro and in vivo studies were conducted to assess transfection efficiency, cytotoxicity, and antitumor efficacy.

Main Results:

• TE demonstrated low cytotoxicity and minimal protein absorption due to abundant hydroxyl groups.
• Optimal TE formulations exhibited significantly higher gene transfection efficiency compared to branched PEI (25 kDa).
• In vivo delivery of antioncogene p53 using TE showed significant tumor inhibition with minimal adverse effects.

Conclusions:

• This work presents a novel, facile method for synthesizing hyperbranched hydroxyl-rich polycations (TE).
• TE serves as a promising nonviral gene carrier with superior transfection performance and safety profile.
• TE holds potential for effective in vivo gene therapy applications, particularly in cancer treatment.