Amplified Self-Immolative Release of Small Molecules by Spatial Isolation of Reactive Groups on DNA-Minimal Architectures

Triggering the release of small molecules in response to unique biomarkers is important for applications in drug delivery and biodetection. Due to low quantities of biomarker, amplifying release is necessary to gain appreciable responses. Nucleic acids have been used for both their biomarker-recognition properties and as stimuli, notably in amplified small-molecule release by nucleic-acid-templated catalysis (NATC). The multiple components and reversibility of NATC, however, make it difficult to apply in vivo. Herein, we report the use of the hybridization chain reaction (HCR) for the amplified, conditional release of small molecules from standalone nanodevices. We couple HCR with a DNA-templated reaction resulting in the amplified, immolative release of small molecules. We integrate the HCR components into single nanodevices as DNA tracks and spherical nucleic acids, spatially isolating reactive groups until triggering. This could be applied to biosensing, imaging, and drug delivery.