Biocompatible Infinite-Coordination-Polymer Nanoparticle-Nucleic-Acid Conjugates for Antisense Gene Regulation

Herein, we report the synthesis of DNA‐functionalized infinite‐coordination‐polymer (ICP) nanoparticles as biocompatible gene‐regulation agents. ICP nanoparticles were synthesized from ferric nitrate and a ditopic 3‐hydroxy‐4‐pyridinone (HOPO) ligand bearing a pendant azide. Addition of FeIII to a solution of the ligand produced nanoparticles, which were colloidally unstable in the presence of salts. Conjugation of DNA to the FeIII–HOPO ICP particles by copper‐free click chemistry afforded colloidally stable nucleic‐acid nanoconstructs. The DNA–ICP particles, when cross‐linked through sequence‐specific hybridization, exhibited narrow, highly cooperative melting transitions consistent with dense DNA surface loading. The ability of the DNA–ICP particles to enter cells and alter protein expression was also evaluated. Our results indicate that these novel particles carry nucleic acids into mammalian cells without the need for transfection agents and are capable of efficient gene knockdown. DNA‐modifizierte Nanopartikel aus kontinuierlichen Koordinationspolymeren (ICPs) wurden durch eine einfache Methode synthetisiert, um biokompatible Genregulatoren zu erhalten. Die Eisen(III)‐basierten ICP‐Nanopartikel wurden in Wasser synthetisiert und durch eine kupferfreie Klickreaktion direkt an Oligonukleotide konjugiert. Die Konjugate können in Zellen eintreten und ohne Transfektionsagentien die Genregulation von Antisense‐Genen bewirken.