Spleen Targeting Nucleic Acid Delivery Vector Based on Metal-Organic Frameworks.

Area of Science:

• Biomaterials Science
• Nanotechnology
• Drug Delivery

Background:

• Nucleic acid therapies offer advantages over protein-based drugs but require effective delivery vectors.
• Current nonviral vectors like liposomes often accumulate in the liver, limiting their use for extrahepatic targets.
• Developing targeted delivery systems is crucial for advancing nucleic acid-based medicine.

Purpose of the Study:

• To develop a novel spleen-targeting delivery vector for nucleic acids.
• To create a metal-organic framework (MOF)-based nanoparticle system for enhanced nucleic acid delivery.
• To evaluate the efficacy and biodistribution of the novel vector compared to traditional liposomes.

Main Methods:

• Synthesized nanoscale zeolitic imidazolate framework (ZIF) nanoparticles encapsulating plasmids via coprecipitation.
• Co-encapsulated poly(ether imide) (PEI) and polyvinylpyrrolidone (PVP) to improve nanoparticle stability and dispersion.
• Investigated in vitro transfection mechanisms, primarily clathrin-mediated and caveolae-mediated endocytosis.
• Performed biodistribution studies in mice to assess spleen and extrahepatic organ accumulation.

Main Results:

• The ZIF-based nanoparticles demonstrated efficient in vitro transfection.
• Biodistribution studies revealed significant spleen accumulation (46%) of the nanoparticles, outperforming liposomes.
• The vector successfully delivered plasmids to extrahepatic organs, enabling protein synthesis and immune response induction.

Conclusions:

• Zeolitic imidazolate framework (ZIF)-based nanoparticles represent a viable and effective system for spleen-targeting nucleic acid delivery.
• This novel vector system shows potential for overcoming the limitations of liposomes in extrahepatic nucleic acid therapies.
• The developed MOF-based nanoparticles offer a new strategy for targeted delivery of nucleic acids to the spleen and other extrahepatic sites.