Unzipping and binding of small interfering RNA with single walled Carbon Nanotube: a platform for small interfering RNA delivery

In an effort to design efficient platform for siRNA delivery, we combine all atom classical and quantum simulations to study the binding of small interfering RNA (siRNA) by pristine single wall carbon nanotube (SWCNT). Our results show that siRNA strongly binds to SWCNT surface via unzipping its base-pairs and the propensity of unzipping increases with the increase in the diameter of the SWCNTs. The unzipping and subsequent wrapping events are initiated and driven by van der Waals interactions between the aromatic rings of siRNA nucleobases and the SWCNT surface. However, MD simulations of double strand DNA (dsDNA) of the same sequence show that the dsDNA undergoes much less unzipping and wrapping on the SWCNT in the simulation time scale of 70 ns. This interesting difference is due to smaller interaction energy of thymidine of dsDNA with the SWCNT compared to that of uridine of siRNA, as calculated by dispersion corrected density functional theory (DFT) methods. After the optimal binding of siRNA to SWCNT, the complex is very stable which serves as one of the major mechanisms of siRNA delivery for biomedical applications. Since siRNA has to undergo unwinding process with the effect of RNA- induced silencing complex, our proposed delivery mechanism by SWCNT possesses potential advantages in achieving RNA interference (RNAi).

💡 Research Summary

This paper explores the interaction between small interfering RNA (siRNA) and single-walled carbon nanotubes (SWCNTs), aiming to design an efficient platform for siRNA delivery. Through all-atom classical and quantum simulations, researchers discovered that siRNA strongly binds to SWCNT surfaces through unzipping its base-pairs, with this propensity increasing as the diameter of the SWCNT increases. The binding mechanism is primarily driven by van der Waals interactions between the aromatic rings of siRNA nucleobases and the SWCNT surface. This interaction initiates and drives the unzipping and subsequent wrapping events of siRNA on SWCNTs. However, double-strand DNA (dsDNA) with the same sequence shows much less unzipping and wrapping on SWCNT within a 70ns simulation timeframe, due to its thymidine having lower interaction energy with SWCNT compared to uridine in siRNA, as calculated by dispersion-corrected density functional theory methods. After optimal binding of siRNA to SWCNT, the complex is highly stable, serving as one of the major mechanisms for siRNA delivery in biomedical applications. Since siRNA needs to undergo an unwinding process due to RNA-induced silencing complexes (RISCs), the proposed delivery mechanism by SWCNT offers potential advantages in achieving RNA interference (RNAi). This study highlights the promising role of SWCNTs in enhancing the efficiency and stability of siRNA delivery systems for therapeutic applications.