Maximizing the Intracellular Delivery of Spherical Nucleic Acids by Engineering Oligonucleotide Sequence

Narayan, Suguna ;   Choi, Chung Hang J ;   Hao, Liangliang ;   Calabrese, Colin ;   Mirkin, Chad

Spherical nucleic acids (SNAs), consisting of densely packed, highly oriented oligonucleotides attached to the surface of nanoparticles, are able to overcome many challenges that are typical of nucleic acid delivery. Recently, it has been shown that SNAs enter cells by interacting with class A scavenger receptors (SR-A). Poly(guanosine) oligonucleotides are natural ligands for SR-A, and by constructing SNAs that are enriched in guanosine, we were able to maximize the delivery of SNAs with a therapeutic payload into cancer cells. This work presents an effective strategy to maximize the intracellular delivery of SNAs and is potentially applicable to other nanoparticle systems, thus establishing an important design consideration for nanoparticle-based intracellular delivery of therapeutics.