Inter-molecular β-sheet structure facilitates lung-targeting siRNA delivery

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Pharmacology

Background:

• Passive targeting utilizes tissue characteristics for drug delivery.
• Nanoparticles accumulate in the liver and spleen, while microparticles are trapped in the lungs.

Purpose of the Study:

• To develop a lung-targeting siRNA delivery system using a novel peptide.
• To exploit the size-dependent entrapment of particles in lung capillaries.

Main Methods:

• Designed and studied a multi-domain peptide (K-β) forming intermolecular β-sheet structures.
• Formed stable K-β peptide-siRNA complexes (60 nm).
• Investigated in vivo behavior and gene silencing in mice after intravenous injection.

Main Results:

• K-β peptide-siRNA complexes formed micron-sized aggregates in vivo, entrapping within lung capillaries.
• Achieved passive accumulation and gene silencing in the lungs.
• Observed siRNA enrichment and gene silencing in the liver as well.
• Aggregates showed potential for dissociation, mitigating pulmonary embolism.

Conclusions:

• The K-β peptide facilitates size-dependent lung targeting of siRNA via aggregation.
• This peptide-based drug delivery strategy demonstrates low toxicity, biodegradability, and programmability.
• Shows significant potential for in vivo applications in lung-targeted therapies.