Biocompatible infinite-coordination-polymer nanoparticle-nucleic-acid conjugates for antisense gene regulation

Colin M. Calabrese, Timothy J. Merkel, William E. Briley, Pratik S. Randeria, Suguna P. Narayan, Jessica L. Rouge, David A. Walker, Alexander W. Scott, Chad A. Mirkin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

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 crosslinked 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.

Original languageEnglish (US)
Pages (from-to)476-480
Number of pages5
JournalAngewandte Chemie - International Edition
Volume54
Issue number2
DOIs
StatePublished - Jan 7 2015

Keywords

  • Antisense gene regulation
  • Coordination polymers
  • Gene knockdown
  • Iron nanoparticles

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)

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