Multilayered Activatable Nanoprobe for Ultra-Bright Tumor Imaging.

The development of tumor targeted probes with strong signal and high contrast is always challenging in cancer imaging. Here, a unique multilayered activatable nanoprobe (MAN) is prepared to fulfill this long-standing goal. MAN adopts a versatile layer-by-layer fabrication technique that sequentially assembles multifunctional polyelectrolytes onto nanoparticles via charge-charge interaction. Unlike the common one-probe-one-fluorochrome construct, MAN offers a dramatic fluorescence enhancement by transporting a large quantity of quenched fluorochromes for maximal signal and contrast. Excellent signal amplification and retention with negligible cytotoxicity is observed in cell study. Upon systemic injection into mice, MAN quickly accumulates in tumor and its fluorescent signal is turned on by proteases overexpressed in tumors, resulting in >700% tumor-to-normal-tissue contrast. This multilayered fabrication provides a simple and powerful universal platform to design sensitive tumor imaging probes.