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A dual-emissive-materials design concept enables tumour hypoxia imaging


Luminescent materials are widely used for imaging and sensing owing to their high sensitivity, rapid response and facile detection by many optical technologies1. Typically materials must be chemically tailored to achieve intense, photostable fluorescence, oxygen-sensitive phosphorescence or dual emission for ratiometric sensing, often by blending two dyes in a matrix. Dual-emissive materials combining all of these features in one easily tunable molecular platform are desirable, but when fluorescence and phosphorescence originate from the same dye, it can be challenging to vary relative fluorescence/phosphorescence intensities for practical sensing applications. Heavy-atom substitution2 alone increases phosphorescence by a given, not variable amount. Here, we report a strategy for modulating fluorescence/phosphorescence for a single-component, dual-emissive, iodide-substituted difluoroboron dibenzoylmethane-poly(lactic acid) (BF2dbm(I)PLA) solid-state sensor material. This is accomplished through systematic variation of the PLA chain length in controlled solvent-free lactide polymerization3 combined with heavy-atom substitution2. We demonstrate the versatility of this approach by showing that films made from low-molecular-weight BF2dbm(I)PLA with weak fluorescence and strong phosphorescence are promising as ‘turn on’ sensors for aerodynamics applications4, and that nanoparticles fabricated from a higher-molecular-weight polymer with balanced fluorescence and phosphorescence intensities serve as ratiometric tumour hypoxia imaging agents.

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Figure 1: Synthesis and solid-state emission of BF2dbm(I)PLA (P1–P3).
Figure 2: Oxygen sensitivity for P1 BF2dbm(I)PLA film.
Figure 3: Tumour hypoxia imaging with P2 BF2dbm(I)PLA nanoparticles.

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We thank the National Science Foundation (C.L.F.: CHE 0718879), the Department of Defense (G.M.P.: Postdoctoral Fellowship W81XWH-07-1-0355) and the NIH (M.W.D.: R01CA40355) for support for this research. We are also grateful to the UVA NanoSTAR Institute and the UVA Cancer Center through the James and Rebecca Craig Foundation and the NCI Cancer Center Support Grant P30 CA44579 for supporting our efforts to develop and test BNPs as biomedical imaging agents. We thank J. N. Demas for helpful discussions and R. E. Evans for assistance.

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G.Z and C.L.F. are responsible for materials design, synthesis and characterization and manuscript preparation. G.M.P. and M.W.D. are responsible for tumour hypoxia imaging studies and data analysis.

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Correspondence to Cassandra L. Fraser.

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Zhang, G., Palmer, G., Dewhirst, M. et al. A dual-emissive-materials design concept enables tumour hypoxia imaging. Nature Mater 8, 747–751 (2009).

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