Abstract
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 language | English |
|---|---|
| Pages (from-to) | 1107-1113 |
| Number of pages | 7 |
| Journal | Chemical Science |
| Volume | 11 |
| Issue number | 4 |
| Early online date | 27 Nov 2019 |
| DOIs | |
| Publication status | Published - 28 Jan 2020 |
Funding
All animal experiments were carried out under the Guidelines for Care and Use of Laboratory Animals of Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences and approved by the Institutional Animal Care and Use Committee (IACUC) of SIMM (Shanghai, China). RAW 264.7 and HeLa were obtained from ATCC (American Type Culture Collection). The authors thank the National Natural Science Foundation of China (Nos. 21788102, 91853201, 21722801, 81673489, 31871414 and U1832144), the Shanghai Municipal Science and Technology Major Project (No. 2018SHZDZX03), the International Cooperation Program of Shanghai Science and Technology Committee (No. 17520750100), the Youth Innovation Promotion Association of Chinese Academy of Sciences (No. 2017319), the Shanghai Science and Technology Committee (No. 19410712600) and the Fundamental Research Funds for the Central Universities (222201717003) for nancial support. TDJ wishes to thank the Royal Society for a Wolfson Research Merit Award. The work in Austin was supported by the National Institutes of Health (RO1 GM103790) and the Robert A. Welch Foundation (F-0018). We would like to thank the EPSRC and the University of Bath for funding for ACS and MLO for studentships. MW would like to thank the EPSRC for funding (i) EP/ L016354/1 and CDT in Sustainable Chemical Technologies.
ASJC Scopus subject areas
- General Chemistry
