Intercalation-mediated nucleic acid nanoparticles for siRNA delivery

Tremendous effort has been made to improve stability and delivery efficacy of small RNA therapeutics. However, nearly all current nano-encapsulation carriers utilize the critical balance between only two interacting parameters: RNA-binding electrostatic interactions and nanoparticle-stabilizing hydrophobic interactions. We report the development of intercalation-meditated nucleic acid (IMNA) nanoparticles, which utilize intercalation as a third interaction to enhance small RNA delivery. This toolbox expansion of interaction parameters may inspire the use of additional forces in nanoparticle drug carriers to increase potency and stability.