Gene Therapy with Chitosan Nanoparticles: Modern Formulation Strategies for Enhancing Cancer Cell Transfection.

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Molecular Biology

Background:

• Gene therapy utilizes exogenous genetic material for therapeutic modification of gene expression or cellular properties.
• Non-viral gene delivery systems, particularly chitosan-based nanoparticles, are increasingly favored over viral vectors due to their improved safety profile.
• Chitosan nanoparticles are widely explored for nucleic acid delivery, with a focus on targeting cancer cells.

Purpose of the Study:

• To review recent formulation strategies for enhancing chitosan nanoparticles for gene delivery.
• To address limitations of chitosan nanoparticles, including poor solubility, non-specificity, and inefficient endosomal escape.
• To provide insights into advancing chitosan-based gene delivery systems for improved therapeutic efficacy, particularly in cancer therapy.

Main Methods:

• Critical evaluation of recent formulation approaches for chitosan nanoparticles.
• Analysis of strategies to improve chitosan nanoparticle stability, targeting specificity, cellular uptake, and endosomal escape.
• Review of literature focusing on chitosan-based gene delivery systems for cancer therapy.

Main Results:

• Chitosan's positively charged amino groups facilitate stable nanocomplex formation with nucleic acids and enhance cellular uptake.
• Challenges remain, including poor solubility at physiological pH, lack of cancer cell specificity, and inefficient endosomal escape, limiting transfection efficiency.
• Various strategies are being investigated to overcome these limitations and enhance nanoparticle functionality.

Conclusions:

• Enhancing chitosan nanoparticle functionality is crucial for improving gene delivery efficacy.
• Targeted modifications can improve stability, specificity, cellular uptake, and endosomal escape of chitosan-based gene delivery systems.
• Further advancements in chitosan nanoparticle formulations hold significant promise for effective cancer gene therapy.