Silica Nanoparticles with Virus-Mimetic Spikes Enable Efficient siRNA Delivery In Vitro and In Vivo

Area of Science:

• Biotechnology
• Nanotechnology
• Gene Therapy

Background:

• Oligonucleotide-based therapies show promise but face delivery challenges.
• Current viral and lipid vectors have limitations like immune clearance or strict storage needs.

Purpose of the Study:

• To develop novel, safe, and efficient delivery vectors for oligonucleotide-based therapies.
• To create virus-mimetic spike silica nanoparticles (NH2-SSNs) with controlled spike lengths.

Main Methods:

• Fabrication of amino-modified virus-mimetic spike silica nanoparticles (NH2-SSNs) via a one-pot, surfactant-free method.
• Evaluation of NH2-SSNs' delivery performance and biosafety in various cell types and mice.
• Investigation of cellular uptake mechanisms, including spike-dependent docking and dynamin-dependent endocytosis.

Main Results:

• NH2-SSNs exhibited excellent delivery performance and biosafety across diverse cell types and in mice.
• The nanoparticles efficiently encapsulated RNAs, protected them from degradation, and facilitated early endosome escape.
• Cellular entry was mediated by spike-dependent membrane docking and dynamin-dependent endocytosis.

Conclusions:

• NH2-SSNs serve as highly effective vehicles for nucleic acid delivery, mimicking viral internalization.
• These nanoparticles offer significant advantages over lipid nanovectors in terms of storage, transportation, modification, and large-scale production for gene therapy.