Near-infrared optical imaging of B16 melanoma cells via low-density lipoprotein-mediated uptake and delivery of high emission dipole strength tris[(porphinato)zinc(II)] fluorophores.
Meso-to-meso ethyne-bridged tris[(porphinato)zinc(II)] (PZn(3)) near-infrared (NIR) fluorophores (lambda(em)(max) approximately 800 nm) can be rendered sufficiently amphiphilic to enable their facile incorporation into the hydrophobic core of the apo form of low-density lipoprotein (apo-LDL). These NIR fluorophores are notable in that they manifest low energy excited states polarized exclusively along the long axis of the supermolecule, broad spectral coverage of the visible and high energy NIR spectral domains, intense S(0)-->S(1) transition moments, and comparably large S(1)-->S(0) emission dipole strengths. The reconstituted LDL(PZn(3)) proteins can be used to deliver rapidly hundreds of copies of PZn(3) to a given murine B16 melanoma cell via LDL receptor-mediated endocytosis. PZn(3)-based NIRFs and their corresponding LDL(PZn(3)) proteins have been shown to display minimal cytotoxicity. Confocal NIR fluorescence microscopy evinces that B16 cells can be imaged at very low doses (approximately nM) of NIRF. The highly attractive photophysical properties of PZn(3) and closely related chromophores, coupled with their lack of toxicity and compatibility with uptake into apo-LDL and subsequent rapid delivery to B16 cells via LDLr-mediated endocytosis, suggest the potential utility of this platform for NIR optical imaging of cancer cells in vivo.
Wu, SP; Lee, I; Ghoroghchian, PP; Frail, PR; Zheng, G; Glickson, JD; Therien, MJ
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