Polymer beacons for luminescence and magnetic resonance imaging of DNA delivery

Joshua M. Bryson, Katye M. Fichter, Wen Jang Chu, Jing Huei Lee, Jing Li, Louis A. Madsen, Patrick M. McLendon, Theresa M. Reineke

Research output: Contribution to journalArticlepeer-review

84 Scopus citations

Abstract

The delivery of nucleic acids with polycations offers tremendous potential for developing highly specific treatments for various therapeutic targets. Although materials have been developed and studied for polynucleotide transfer, the biological mechanisms and fate of the synthetic vehicle has remained elusive due to the limitations with current labeling technologies. Here, we have developed polymer beacons that allow the delivery of nucleic acids to be visualized at different biological scales. The polycations have been designed to contain repeated oligoethyleneamines, for binding and compacting nucleic acids into nanoparticles, and lanthanide (Ln) chelates [either luminescent europium (Eu3+) or paramagnetic gadolinium (Gd3+)]. The chelated Lns allow the visualization of the delivery vehicle both on the nm/μm scale via microscopy and on the sub-mm scale via MRI. We demonstrate that these delivery beacons effectively bind and compact plasmid (p)DNA into nanoparticles and protect nucleic acids from nuclease damage. These delivery beacons efficiently deliver pDNA into cultured cells and do not exhibit toxicity. Micrographs of cultured cells exposed to the nanoparticle complexes formed with fluorescein-labeled pDNA and the europium-chelated polymers reveal effective intracellular imaging of the delivery process. MRI of bulk cells exposed to the complexes formulated with pDNA and the gadolinium-chelated structures show bright image contrast, allowing visualization of effective intracellular delivery on the tissuescale. Because of their versatility, these delivery beacons posses remarkable potential for tracking and understanding nucleic acid transfer in vitro, and have promise as in vivo theranostic agents.

Original languageEnglish (US)
Pages (from-to)16913-16918
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number40
DOIs
StatePublished - Oct 6 2009

Keywords

  • Intracellular imaging
  • Lanthanide
  • Nucleic acid delivery
  • Theranostic

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