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

Hai Hao Han, Adam C. Sedgwick, Ying Shang, Na Li, Tingting Liu, Bo Han Li, Kunqian Yu, Yi Zang, James T. Brewster, Maria L. Odyniec, Maria Weber, Steven D. Bull, Jia Li, Jonathan L. Sessler, Tony D. James, Xiao Peng He, He Tian

Research output: Contribution to journalArticlepeer-review

50 Citations (SciVal)


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-versusPinkment-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.

Original languageEnglish
Pages (from-to)1107-1113
Number of pages7
JournalChemical Science
Issue number4
Early online date27 Nov 2019
Publication statusPublished - 28 Jan 2020

ASJC Scopus subject areas

  • General Chemistry


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