Protein encapsulation: a new approach for improving the capability of small-molecule fluorogenic probes.

Herein, we report a protein-based hybridization strategy that exploits the host-guest chemistry of HSA (human serum albumin) to solubilize the otherwise cell impermeable ONOO fluorescent probe . Formation of a / supramolecular hybrid was confirmed by SAXS and solution-state analyses. This / hybrid provided an enhanced fluorescence response towards ONOO alone, as determined by experiments. The / hybrid was also evaluated in RAW 264.7 macrophages and HeLa cancer cell lines, which displayed an enhanced cell permeability enabling the detection of SIN-1 and LPS generated ONOO and the imaging of acute inflammation in LPS-treated mice. A remarkable 5.6 fold (RAW 264.7), 8.7-fold (HeLa) and 2.7-fold increased response was seen relative to alone at the cellular level and , respectively. We anticipate that HSA/fluorescent probe hybrids will soon become ubiquitous and routinely applied to overcome solubility issues associated with hydrophobic fluorescent imaging agents designed to detect disease related biomarkers.