Novel bionic inspired nanosystem construction for precise delivery of mRNA

Area of Science:

• Biotechnology
• Nanomedicine
• Drug Delivery

Background:

• Messenger RNA (mRNA) therapeutics show promise but face delivery challenges, particularly to liver tissues.
• Efficient and targeted delivery of mRNA is crucial for clinical translation of mRNA-based vaccines and therapies.

Purpose of the Study:

• To develop and evaluate novel virus-like mesoporous silica nanoparticles (V-SiO2) for enhanced intracellular mRNA delivery.
• To investigate the efficacy of surface-modified nanoparticles (V-SiO2-P/LB) for liver-targeted mRNA delivery both in vitro and in vivo.

Main Methods:

• Synthesis of virus-like mesoporous silica nanoparticles (V-SiO2).
• Surface modification with polyethylenimine (PEI) and subsequent mRNA loading (m@V-SiO2-P).
• Encapsulation with a lipid bilayer (LB) to form bionic-like nanoparticles (m@V-SiO2-P/LB).

Main Results:

• The V-SiO2-P/LB nanoparticles demonstrated superior mRNA delivery to hepatocytes compared to traditional liposomes (m@LNPs).
• PEI modification enhanced mRNA binding and facilitated intracellular lysosomal escape.
• The V-SiO2-P/LB system exhibited a significantly longer blood circulation time (7 h) than m@LNPs (4.2 h).

Conclusions:

• The developed V-SiO2-P/LB nanosystem represents a highly efficient platform for intracellular mRNA delivery.
• This bionic-like nanoparticle design overcomes key limitations in current mRNA therapy delivery.
• The nanosystem's potential extends to various orthotopic injection sites beyond the liver.