Here we wish to report the synthesis of core/shell Fe/Fe3O4 nanoparticle-based �light switches� for the quantitative determination of cancer-specific proteases in breast cancer tissue via in-vivo fluorescence microscopy and optical tomography. This nanoplatform consists of a series of cyanine dyes that are chemically linked to core/shell Fe/Fe3O4 nanoparticles via protease-selective consensus (cleavage) peptide sequences. Monodisperse Fe/Fe3O4-nanoparticles were developed by NanoScale Corporation, and further functionalized by dopamine-based oligoethylene glycol ligands featuring glycine tips. Ten different cancer specific protease selective consensus sequences have been synthesized with sufficient purity by adapting a solid phase peptide synthesis protocol. A series of cyanine dyes, hydrophilic as well as hydrophobic, featuring fluorescence bands that do not interfere with the autofluorescence of mammalian tissue and blood, have been synthesized in multi-hundred milligrams with high purity. The cyanine dyes were conjugated to the consensus sequences before cleaving the peptide sequence from the solid phase, which enable an easy way to obtain fluorescence-cyanine-dye labeled peptide sequence in high purity without tedious purification process. Finally, the cyanine dye labeled consensus sequences were linked to the nanoparticle by EDC coupling of the C-terminal of the peptide sequence and the glycine tips on the surface of the nanoparticles. In this nanoplatform, the tether between the nanoparticle and a specific cyanine dye was carefully designed and programmed so that the length of the tether falls into the range of the F�rster-radius of the cyanine dye, where the cyanine dye experiences rapid fluorescence quenching by the plasmon of the Fe(0)-core. Our preliminary results show that the �light switch� could be turned on with the concentration of active enzymes down to 5 x 10-14M. Currently, this nanoplatform is being tested for optically imaging the boundaries of 4T1 breast cancer tumors in BALB/c mice.

Synthesis of core/shell Fe/Fe<sub>3</sub>O<sub>4</sub> nanoparticle-based “light switches” for determination of cancer-specific proteases in breast cancer tissue

242nd National Meeting (2011)

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