Reductively Cleavable Nanocaplets for siRNA Delivery by Template-Assisted Oxidative Polymerization

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Gene Delivery

Background:

• siRNA delivery is crucial for gene silencing therapies.
• Developing efficient and safe siRNA carriers remains a challenge.
• Guanidinium groups can enhance cellular uptake and endosomal escape.

Purpose of the Study:

• To synthesize water-soluble dithiol monomers with multiple guanidinium units.
• To develop a template-assisted oxidative polymerization method for siRNA packaging.
• To evaluate the cellular uptake and gene silencing efficacy of the siRNA-loaded nanocapsules.

Main Methods:

• Synthesis of telechelic dithiol monomers with guanidinium units.
• Template-assisted oxidative polymerization using siRNA as a template.
• Characterization of nanocapsule size and siRNA loading.
• In vitro studies on cellular uptake and gene expression suppression.

Main Results:

• Uniform-sized (7 ± 2 nm) nanocapsules encapsulating siRNA were successfully formed.
• The nanocapsules demonstrated efficient cellular uptake in live cells.
• Intracellular depolymerization released siRNA in the reductive cytosolic environment.
• Significant suppression of gene expression was observed.

Conclusions:

• Novel guanidinium-rich polymers enable efficient siRNA packaging and delivery.
• The developed nanocapsules are effective carriers for gene silencing applications.
• This approach offers a promising strategy for therapeutic siRNA delivery.