Controlled Sequential Assembly of DNA Nanoparticles Inside Cells Enabling Mitochondrial Interference

Abstract

AbstractDeveloping artificial material systems to rationally interfere with organelles is emerging as a promising route to regulate the behaviors and fate of cells, thus providing new therapeutic strategies. Herein, a DNA nanoparticles (DNPs)‐based material system is reported, which achieves controlled sequential assembly inside cells, and realizes specific interference toward mitochondria. Two types of DNPs are synthesized via radical polymerization, followed with cascade hybridization chain reaction of hairpin DNA with Cyanine5 (Cy5) for mitochondrial targeting, and with complementary sequences for base pairing, respectively. DNPs with Cy5 (Cy5‐DNPs) first entered cells to target mitochondria, and the other DNPs with complementary sequences entered cells after an interval to sequentially assemble with Cy5‐DNPs into aggregates via base pairing. Mitochondrial interference is achieved, including increased reactive oxygen species, decreased membrane potential, abnormal elevation of Ca2+ level, decreased adenosine triphosphate, and attenuated cellular migration rate. In particular, by regulating the intervals of two types of DNPs entering cells, the mitochondrial interference degree is controllably modulated. This work achieves regulated organelles interference via the precise controlled self‐assembly of DNA nanostructures inside cells, which is envisioned to have great potential in precision biomedicine.