Chemical Composition and Backbone Modifications Define Deformability of Nucleic Acid Nanoparticles

Area of Science:

• Biotechnology
• Nanotechnology
• Materials Science

Background:

• Nucleic acid nanoparticles (NANPs) are programmable platforms for drug delivery.
• Understanding NANP mechanical properties is crucial for optimizing therapeutic applications.

Purpose of the Study:

• To investigate the mechanical properties of DNA, RNA, and hybrid NANP cubes using nanopore analysis.
• To correlate structural and material differences with mechanical deformability at the molecular level.

Main Methods:

• Electrophoretic translocation of NANP cubes through solid-state nanopores.
• All-atom molecular dynamics (MD) simulations to analyze mechanical flexibility.
• Characterization of six-stranded RNA and DNA-based NANPs with cube connectivity.

Main Results:

• DNA cubes deformed and translocated through nanopores, while RNA cubes exhibited significant stiffness.
• Hybrid RNA/DNA cubes showed intermediate mechanical deformability, indicating an additive effect of RNA content.
• Chemical modifications allowed fine-tuning of NANP mechanical properties.

Conclusions:

• Mechanical properties of NANPs are highly dependent on their nucleic acid composition (DNA vs. RNA).
• Nanopore analysis combined with MD simulations provides molecular-level insights into NANP mechanics.
• Tunable mechanical properties of NANPs offer potential for advanced drug delivery systems.