Preparation of Microkernel-Based Mesoporous (SiO2-CdTe-SiO2)@SiO2 Fluorescent Nanoparticles for Imaging Screening and Enrichment of Heat Shock Protein 90 Inhibitors from Tripterygium Wilfordii
Preparation of Microkernel-Based Mesoporous (SiO2-CdTe-SiO2)@SiO2 Fluorescent Nanoparticles for Imaging Screening and Enrichment of Heat Shock Protein 90 Inhibitors from Tripterygium Wilfordii
复制标题
微核介孔(SiO2-CdTe-SiO2)@SiO2荧光纳米粒子的制备用于雷公藤热休克蛋白90抑制剂的成像筛选和富集。
DOI：
10.1021/acs.analchem.7b05295
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发表时间：
2018-05-01
影响因子：
7.4
通讯作者：
Zhu, Dong
中科院分区：
文献类型：
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作者：
Hu, Yue;Miao, Zhao-Yi;Zhu, Dong
目前用于从复杂基质中筛选生物活性分子的配体捕捞不能进行成像筛选。在这里，我们开发了一种新的固相配体钓鱼结合原位成像方案，用于特异性富集和鉴定雷公藤热休克蛋白90（Hsp 90）抑制剂，利用多层和基于微孔的介孔纳米结构，由保护性二氧化硅涂层CdTe量子点（QD）核心和介孔二氧化硅外壳组成，即，微孔介孔（SiO2-CdTe-SiO2）@SiO2荧光纳米粒子（MMFNPs）作为萃取载体和荧光探针。所制备的MMFNPs表现出高度均匀的球形形态，荧光发射的保留，和巨大的化学稳定性。Hsp 90 α-MMFNPs捕获的配体通过基于共聚焦激光扫描显微镜（CLSM）的实时细胞形态成像的初步生物活性进行评估，然后通过质谱（MS）进行鉴定。南蛇藤酚被成功地分离为Hsp 90抑制剂，并且通过Hsp 90 α-MMFNP筛选了另外两种特异性组分，即，结果表明，地美可辛和雷公藤甲素对Hsp 90具有较强的亲和力和抗肿瘤活性，初步确定为Hsp 90的潜在抑制剂。基于MMFNPs的方法为高效、高选择性地成像筛选和发现植物源生物活性分子提供了强有力的平台。
The currently utilized ligand fishing for bioactive molecular screening from complex matrixes cannot perform imaging screening. Here, we developed a new solid-phase ligand fishing coupled with an in situ imaging protocol for the specific enrichment and identification of heat shock protein 90 (Hsp 90) inhibitors from Tripterygium wilfordii, utilizing a multiple-layer and microkernel-based mesoporous nanostructure composed of a protective silica coating CdTe quantum dot (QD) core and a mesoporous silica shell, i.e., microkernel-based mesoporous (SiO2-CdTe-SiO2)@SiO2 fluorescent nanoparticles (MMFNPs) as extracting carries and fluorescent probes. The prepared MMFNPs showed a highly uniform spherical morphology, retention of fluorescence emission, and great chemical stability. The fished ligands by Hsp 90 alpha-MMFNPs were evaluated via the preliminary bioactivity based on real-time cellular morphology imaging by confocal laser scanning microscopy (CLSM) and then identified by mass spectrometry (MS). Celastrol was successfully isolated as an Hsp 90 inhibitor, and two other specific components screened by Hsp 90 alpha-MMFNPs, i.e., demecolcine and wilforine, were preliminarily identified as potential Hsp 90 inhibitors through the verification of strong affinity to Hsp 90 and antitumor bioactivity. The approach based on the MMFNPs provides a strong platform for imaging screening and discovery of plant-derived biologically active molecules with high efficiency and selectivity.