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
Key Laboratory for Advanced Materials, Joint International Research Laboratory of Precision Chemistry and Molecular Engineering, Feringa Nobel Prize Scientist Joint Research Center, School of Chemistry and Molecular Engineering, East China University of Science and Technology 130 Meilong Road Shanghai 200237 P. R. China
National Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences 189 Guo Shoujing Rd. Shanghai 201203 P. R. China
Chem Sci. 2019 Nov 27;11(4):1107-1113. 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 . 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.
在此，我们报告了一种基于蛋白质的杂交策略，该策略利用人血清白蛋白（HSA）的主客体化学性质来溶解原本无法穿透细胞的ONOO荧光探针。通过小角X射线散射（SAXS）和溶液状态分析证实了超分子杂化物的形成。如实验所确定的，这种杂化物对单独的ONOO具有增强的荧光响应。该杂化物还在RAW 264.7巨噬细胞和HeLa癌细胞系中进行了评估，其显示出增强的细胞通透性，能够检测SIN-1和LPS产生的ONOO，并对LPS处理的小鼠中的急性炎症进行成像。在细胞水平上，相对于单独的情况，分别观察到显著的5.6倍（RAW 264.7）、8.7倍（HeLa）和2.7倍的响应增加。我们预计，HSA/荧光探针杂化物很快将变得无处不在，并常规用于克服与旨在检测疾病相关生物标志物的疏水性荧光成像剂相关的溶解性问题。
