Xiangya School of Pharmaceutical Sciences, Central South University , Changsha 410013, China.
Molecular Imaging Program at Stanford (MIPS), Canary Center at Stanford for Cancer Early Detection, Department of Radiology and Bio-X Program, School of Medicine, Stanford University , Stanford, California 94040, United States.
Anal Chem. 2017 Sep 19;89(18):10085-10093. doi: 10.1021/acs.analchem.7b02923. Epub 2017 Sep 7.
Specific detection or imaging protein has high potential to contribute greatly to medical diagnosis, biological research, and therapeutic applications. The level of human serum albumin (HSA) in blood is related to a variety of diseases and thus serves as an important biomarker for fast clinical diagnosis. Here we report the use of aggregation-induced emission (AIE) based supramolecular assembly to design biomolecular responsive smart organic nanomaterials for detection protein HSA. The designed nanoprobes were aggregates of small molecules and silent in fluorescence, but in the presence of HSA they disassembled and produced a clear turn-on fluorescent signal. Of a small library of nanoprobes constructed for HSA detection, structure-optical signaling and screening studies revealed that nanoprobe 7 is the most efficient one. Mechanism studies showed that nanoprobe 7 was bonded with Site I of HSA through the multiple noncovalent interactions. The resultant restriction of intramolecular rotation of nanoprobe 7 in the hydrophobic cavity of HSA induced fluorescent emission, which was validated by competitive binding assays and molecular docking. More importantly, nanoprobe 7 was successfully applied to recognize and quantify HSA in human serum samples. This study demonstrates nanoprobe 7 is a promising tool for clinical real and fast detection of HSA and thus may find many applications, and the molecular assembly based on AIE also opens a new avenue for designing smart nanomaterials for the sensitive and selective detection for varied analytes.
特定蛋白质的检测或成像具有极大的潜力，可以为医学诊断、生物研究和治疗应用做出重大贡献。血液中人类血清白蛋白（HSA）的水平与多种疾病有关，因此是快速临床诊断的重要生物标志物。在这里，我们报告了使用聚集诱导发射（AIE）基超分子组装来设计用于检测蛋白质 HSA 的生物分子响应智能有机纳米材料。设计的纳米探针是小分子的聚集体，在荧光中不发光，但在存在 HSA 的情况下，它们会解组装并产生明显的开启荧光信号。在用于 HSA 检测的小分子纳米探针的小文库中，结构-光学信号和筛选研究表明，探针 7 是最有效的一种。机制研究表明，探针 7 通过多种非共价相互作用与 HSA 的 Site I 结合。在 HSA 的疏水性腔体内，探针 7 的分子内旋转受到限制，从而诱导荧光发射，这通过竞争性结合测定和分子对接得到了验证。更重要的是，探针 7 成功地用于识别和定量人血清样品中的 HSA。这项研究表明，探针 7 是用于临床实际和快速检测 HSA 的有前途的工具，因此可能有许多应用，并且基于 AIE 的分子组装也为设计用于敏感和选择性检测各种分析物的智能纳米材料开辟了新途径。
