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 Fe(III) to a solution of the ligand produced nanoparticles, which were colloidally unstable in the presence of salts. Conjugation of DNA to the Fe(III)-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.
Department of Chemistry Northwestern University, Evanston, IL (USA).
Colin M
CM
Calabrese
International Institute for Nanotechnology Northwestern University, Evanston, IL (USA).
Timothy J
TJ
Merkel
Interdepartmental Biological Sciences Northwestern University, Evanston, IL (USA).
William E
WE
Briley
Department of Biomedical Engineering Northwestern University, Evanston, IL (USA).
Pratik S
PS
Randeria
Department of Biomedical Engineering Northwestern University, Evanston, IL (USA).
Suguna P
SP
Narayan
International Institute for Nanotechnology Northwestern University, Evanston, IL (USA).
Jessica L
JL
Rouge
International Institute for Nanotechnology Northwestern University, Evanston, IL (USA).
David A
DA
Walker
Department of Biomedical Engineering Northwestern University, Evanston, IL (USA).
Alexander W
AW
Scott
Department of Chemistry Northwestern University, Evanston, IL (USA).
Chad A
CA
Mirkin
D016375:Antisense Elements (Genetics); D001672:Biocompatible Materials; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D018625:Microscopy, Atomic Force; D053758:Nanoparticles / Q000737:chemistry*; D009696:Nucleic Acids / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet
D016375:Antisense Elements (Genetics); D001672:Biocompatible Materials; D009696:Nucleic Acids; D011108:Polymers
antisense gene regulation; coordination polymers; gene knockdown; iron; nanoparticles