Development of streptavidin-based nanocomplex for siRNA delivery

Area of Science:

• Biotechnology
• Nanomedicine
• Molecular Biology

Background:

• Alcoholic liver fibrosis involves collagen stabilization by αCP2 protein.
• PCBP2 siRNA demonstrated antifibrotic activity by inhibiting αCP2 in hepatic stellate cells (HSCs).

Purpose of the Study:

• To develop an efficient streptavidin-based nanocomplex for delivering PCBP2 siRNA to HSCs.
• To evaluate the nanocomplex's efficacy, safety, and cellular uptake in treating liver fibrosis.

Main Methods:

• Formation of a multicomponent siRNA nanocomplex using streptavidin, biotinylated siRNA, biotin-cholesterol, and protamine.
• Assessment of nanocomplex cytotoxicity, cellular uptake efficiency in various cell lines (HSCs, Caco-2, PC-3), and PCBP2 mRNA silencing.
• Evaluation of siRNA protection against degradation in serum.

Main Results:

• The nanocomplex (150-250 nm) showed no cytotoxicity in rat HSCs compared to commercial agents.
• Higher cellular uptake was observed in HSCs, suggesting receptor-mediated endocytosis.
• Achieved over 85% silencing of PCBP2 mRNA in HSCs with excellent serum stability.

Conclusions:

• The streptavidin-based nanocomplex is a promising platform for PCBP2 siRNA delivery to HSCs.
• This strategy holds potential for treating liver fibrosis and can be adapted for other diseases.