English

The team of Professor Cai Xiaoxiao from West China School of Stomatology, Sichuan University and State Key Laboratory of oral disease research fabricated a lysosome-activated tetrahedral nanobox for encapsulated siRNA delivery. Their research was published in Advanced Materials

Based on the nature of deoxyribonucleotides and ribonucleotides, the application of oligonucleotides to precise expression regulation of target genes has attracted the attention of an increasing number of dedicated researchers. In this study, the researchers inspired by the original stable space inside the tetrahedral scaffold, a dynamic lysosome-activated tetrahedral nanobox is fabricated for completely encapsulating a short interfering RNA (siRNA) of interest.

The cargo siRNA was designed to be precisely caged into the original stable space inside the tetrahedral scaffold of nanobox. The unique, fully encapsulated loading method significantly protected caged siRNA from enzymatic and serum degradation, and provided enough load-locking force to prevent unexpected detachment of the carrier and cargo at 37 °C. In addition, the nanobox was transferred from a close state to an open state upon the formation of the four-stranded i-motif structure under lysosomal acidic condition. Thus, in cooperation with the temperature-driven active release, siRNA encapsulated in nanobox overcame the final obstacle into the cytoplasm and controllably silenced the target gene.

Conclusively, the nanobox offers a dynamic pH-sensitive confinement delivery system for siRNA and exhibits broad prospects for use as a small RNA carrier in RNA interference therapy.

Gao Yang is the first author of this article, Professor Cai Xiaoxiao is the corresponding author. West China School/Hospital of Stomatology, Sichuan University is the only accomplishment unit for this article.

For more details, please click the link below:

https://onlinelibrary.wiley.com/doi/10.1002/adma.202201731