Biofunctionalized nanoparticles with pH-responsive and cell penetrating blocks for gene delivery

Area of Science:

• Nanomedicine
• Gene Therapy
• Polymer Chemistry

Background:

• Translational gene therapy requires advanced nanoparticulate delivery systems.
• Nanoparticle functionalization can mimic viral particle features using biofunctional moieties.
• Chitosan is a native material with potential for modification.

Purpose of the Study:

• To conjugate cell-penetrating arginine and pH-responsive histidine moieties into chitosan.
• To enhance the physicochemical properties of chitosan for gene delivery.
• To develop efficient and non-cytotoxic nanocarriers for cancer gene therapy.

Main Methods:

• Conjugation of arginine and histidine to chitosan polymer backbone.
• Characterization of amino acid coupling using 2D TOCSY NMR and Fourier transform infrared spectroscopy.
• Complexation with plasmid DNA and self-assembly into nanoparticles, followed by characterization of size, morphology, and surface charge.

Main Results:

• Successful synthesis of chitosan-histidine-arginine (CH-H-R) polymer confirmed by spectroscopy.
• Formation of stable 105 nm spherical nanoparticles with positive surface charge.
• Efficient cellular internalization, significantly higher transfection efficiency than unmodified chitosan, and no observed cytotoxicity.
• Demonstrated preferential escape from lysosomal pathways and nuclear localization of the nanocarriers.

Conclusions:

• The developed CH-H-R nanoparticles are efficient, non-cytotoxic gene delivery vehicles.
• Bioinspired functionalization of chitosan enhances its properties for nanomedicine applications.
• These customizable nanocarriers provide a foundation for advanced cancer gene therapy strategies.