Mechanism for the Endocytosis of Spherical Nucleic Acid Nanoparticle Conjugates

Abstract

This chapter demonstrates that the rapid cellular uptake kinetics and intracellular transport of spherical nucleic acids (SNAs) stem from the arrangement of oligonucleotides into a 3D architecture, which supports their targeting of class A scavenger receptors and endocytosis via a lipid-raft-dependent, caveolae-mediated pathway. These results reinforce the notion that SNAs can serve as therapeutic payloads and targeting structures to engage biological pathways not readily accessible with linear oligonucleotides. SNAs represent an emerging class of nucleic acids distinct from linear nucleic acids in the context of gene regulation. These nanostructures, although polyanionic like their linear counterparts, can naturally traverse the negatively charged cell membrane and enter cells. The cellular uptake kinetics and intracellular transport of SNAs are monitored to determine their primary entry pathway and identify the primary receptor sub-class that mediates their internalization into mammalian cells.