Synthetic polymers are playing an important role in advancing the field of polynucleotide therapeutics.  While many structures have been designed as carriers for DNA and RNA drugs, the mechanisms of nucleic acid transfer into the cell and the fate of the polymeric vehicle has remained elusive.  Here in, we describe the creation of new polycation-based nucleic acid delivery vehicles that contain the lanthanide metals europium and gadolinium.  The polymers have been synthesized by ring-opening  ondensation polymerization of a Boc-protected oligoethyleneamine monomer with diethylenetriamine pentaacetic acid bisanhydride (DTPA-BA) and then chelated with the lanthanide of choice. Europium has been incorporated to track the delivery of nucleic acids within cells on the nm/�m scale as it has a characteristic red  uminescence. The paramagnetic gadolinium analogs were also created to track nucleic acid delivery on the mm-scale within bulk tissues via MRI. The four polymers structures were shown to bind and compact pDNA into polyplexes.  Cells were then exposed to solutions of the polyplexes and the vehicles successfully deliver pDNA intoHeLa cells.  Our results show that that these novel materials can be visualized within individual cells via confocal microscopy (europium analogs) and on the sub-mm scale via MRI (gadolinium analogs). These new �theranostic� polymers offer the ability to deliver their therapeutic and perform diagnostic imaging of the delivery process.

Luminescent and MRI-active polymers for imaging DNA delivery in cells and tissues

239th National Meeting (2010)

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