New Biocompatible Nanohydrogels of Predefined Sizes for Complexing Nucleic Acids.

Area of Science:

• Biomaterials Science
• Nanotechnology
• Gene Therapy

Background:

• Advancements in mRNA protein expression and CRISPR/Cas9 gene editing necessitate improved in vivo nucleic acid delivery systems.
• Current delivery methods face challenges in efficiency and safety for therapeutic applications.

Purpose of the Study:

• To design, synthesize, and characterize novel cross-linked monodispersed nanohydrogels (NHGs) for enhanced nucleic acid delivery.
• To evaluate the potential of these NHGs for in vivo gene delivery and foreign protein expression.

Main Methods:

• Synthesis of NHGs via polymerization of thermo-responsive monomer self-assemblies at high temperatures.
• Chemical reduction of NHGs to achieve a highly positive zeta potential.
• Characterization of NHG size (50-400 nm), zeta potential, and cell toxicity.
• Formation and characterization of NHG-DNA complexes at optimal charge ratios.

Main Results:

• Monodispersed NHGs with controlled sizes (50-400 nm) were successfully synthesized.
• NHGs exhibited a highly positive zeta potential and low inherent cell toxicity.
• Stable NHG-DNA complexes were formed with DNA fully embedded within the NHGs.
• The size of NHG-DNA complexes was tunable and correlated with NHG size.

Conclusions:

• The novel NHGs are promising, non-toxic candidates for nucleic acid delivery.
• Their tunable size and efficient DNA encapsulation support their potential for gene delivery and protein expression applications.
• These findings contribute to the development of advanced nanocarriers for genetic medicine.