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

• Published in: Chemical science (Cambridge) 2020, Vol.11 (4), p.1107-1113
• Main Authors: Han, Hai-Hao, Sedgwick, Adam C., Shang, Ying, Li, Na, Liu, Tingting, Li, Bo-Han, Yu, Kunqian, Zang, Yi, Brewster, James T., Odyniec, Maria L., Weber, Maria, Bull, Steven D., Li, Jia, Sessler, Jonathan L., James, Tony D., He, Xiao-Peng, Tian, He
• Format: Article
• Language: English
• Subjects: Biomarkers; Chemistry; Fluorescent indicators; Fluoroscopic imaging; Macrophages; Mass spectra; Medical imaging; NMR; Nuclear magnetic resonance; Organic chemistry; Proteins; Serum albumin; Supramolecular compounds
• ISSN: 2041-6520; 2041-6539
• DOI: 10.1039/c9sc03961a

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 Pinkment-OAc . Formation of a HSA / Pinkment-OAc supramolecular hybrid was confirmed by SAXS and solution-state analyses. This HSA / Pinkment-OAc hybrid provided an enhanced fluorescence response towards ONOO − versus Pinkment-OAc alone, as determined by in vitro experiments. The HSA / Pinkment-OAc 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 in vivo 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 Pinkment-OAc alone at the cellular level and in vivo , 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.