Zwitterionic lipid nanoparticles for efficient siRNA delivery and hypercholesterolemia therapy with rational charge self-transformation.

Rationale: Effective delivery of small interfering RNA (siRNA) remains a significant challenge in treating hypercholesterolemia due to biocompatibility, cellular uptake, and endosomal escape issues. Rational regulation of carrier surface charge contributes to efficient siRNA delivery in vivo.

Methods

This study introduces zwitterionic lipid nanoparticles (ZwiLNPs) as a novel solution to these challenges. By leveraging the unique properties of zwitterionic polymers, we achieved robust siRNA encapsulation and targeted delivery. The design of ZwiLNPs facilitates charge self-transformation in response to physiological conditions, which enhances their biocompatibility and cellular uptake efficiency. Result: In vivo studies demonstrated significant liver-targeting capabilities of ZwiLNPs, with improved endosomal escape following cellular internalization. Comparative analyses confirmed that ZwiLNPs outperform conventional lipid nanoparticles in terms of both cellular uptake and endosomal release.

Conclusion

These findings position ZwiLNPs as a promising platform for RNA interference therapies, particularly for hypercholesterolemia and other lipid-related disorders.