The Dynamic, Motile and Deformative Properties of RNA Nanoparticles Lead to Efficient Tumor Vasculature Targeting , Fast Renal Excretion and Rapid Body Clearance

26 September 2022 13:45 - 14:15

  • RNA nanoparticles are motile, dynamic and deformative materials that enable them to squeeze themselves through capillary to reach cancer vasculature & through the kidney glomerulus to quickly enter the urine
  • RNA nanoparticles can reach tumors fast facilitate by both the passive (amoeba property) and active (ligand-assisted) cancer-targeting effect. The fast and high efficient tumor targeting leads to high efficiency
  • The fast renal excretion and rapid body clearance resulted in low or no toxicity. The negative charge of RNA nanoparticles makes them not bind to the normal cell and not enter the organs
  • The 20-30 nm in size ensure that they are not grasped by macrophages, thus reaching the tumor efficiently
  • RNA nanoparticles can make Insoluble natural or chemical drugs soluble
A large number of noncoding RNAs have key roles in the regulation of cellular functions. The dynamic nature of RNA leads to its motion and deformation behavior. These conformational transitions, such as breathing within the complementary area, pseudoknot formation at the 2D level; induced fitting by substrate interaction, conformational capture by key and lock, and shifting in base pairing all are important for their biological functions including tissue binding, cell entry, gene regulation, and protein translation. Their dynamics, catalytic and motile features have led to the belief that RNA is the origin of life. We recently reported that the rubbery, amoeba and shape-shifting properties of RNA nanoparticles enhance their penetration through leaky blood capillary, leading to efficient accumulation in tumor vasculature. These dynamic, motile, and deformable properties of the RNA nanoparticles also enable the RNA nanoparticles to pass through the glomerulus, overcoming the filtration size limitation, resulting in rapid renal excretion and fast body clearance, therefore low or no toxicity. The performance of RNA nanoparticles can be further improved by incorporating cancer-targeting ligands. The inherent negative properties of RNA charge reduce nonspecific cell binding and organ retention due to the repulsion with the cell membrane which is also negatively charged. The multivalent nature of RNA nanoparticles allows for multi functionalities, which can be applied as an approach to overcome drug resistance. In addition to favourable biodistribution characteristics, RNA nanoparticles have other unique properties including self-assembly, programmable synthesis, advantageous size; antigenicity free, large volume distribution, CMC ease, solubilizing drugs, and high payload. All of these make them an excellent material for pharmaceutical applications. RNA drug has become the third milestone in pharmaceutical drug development!

Professor Peixuan Guo, Sylvan Frank Endowed Chair in Pharmaceutics and Drug Delivery, The Ohio State University