Selective detection of phospholipids using molecularly imprinted fluorescent sensory core-shell particles
Selective detection of phospholipids using molecularly imprinted fluorescent sensory core-shell particles
复制标题
使用分子印迹荧光传感核壳颗粒选择性检测磷脂
DOI：
10.1038/s41598-020-66802-3
复制
发表时间：
2020-06-18
影响因子：
4.6
通讯作者：
Sellergren, Borje
中科院分区：
文献类型：
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作者：
Li, Qianjin;Shinde, Sudhirkumar;Sellergren, Borje
1-磷酸鞘氨醇（S1 P）是一种生物活性鞘脂，具有广泛的活性，与其在G蛋白偶联受体信号传导中的作用相关。由于这种脂质的低丰度和缺乏稳健的亲和力测定或传感器，因此监测这种脂质的细胞内和细胞外水平具有挑战性。我们在这里报告荧光传感核壳分子印迹聚合物（MIP）颗粒响应于近生理相关水平的S1 P和S1 P受体调节剂磷酸芬戈莫德（FP）在加标的人血清样品。使用FP的四丁基铵（TBA）盐或磷脂酸（DPPA·Na）作为模板与可聚合硝基苯并恶二唑（NBD）-脲单体组合实现印迹，所述可聚合硝基苯并恶二唑（NBD）-脲单体具有捕获磷酸阴离子和发出其存在的信号的双重作用。使用乙二醇二甲基丙烯酸酯（EGDMA）作为交联剂从约300 nm RAFT改性的二氧化硅核颗粒接枝单体，得到10-20 nm厚的壳，其在水性缓冲介质中对靶向脂质S1 P和DPPA显示选择性荧光响应。在加标血清样品上证明了传感颗粒用于监测血清中S1 P的潜在用途，证明线性范围为18-60 µM，检测限为5.6 µM，该值与生物标志物的血浆浓度范围相同。
Sphingosine-1-phosphate (S1P) is a bioactive sphingo-lipid with a broad range of activities coupled to its role in G-protein coupled receptor signalling. Monitoring of both intra and extra cellular levels of this lipid is challenging due to its low abundance and lack of robust affinity assays or sensors. We here report on fluorescent sensory core-shell molecularly imprinted polymer (MIP) particles responsive to near physiologically relevant levels of S1P and the S1P receptor modulator fingolimod phosphate (FP) in spiked human serum samples. Imprinting was achieved using the tetrabutylammonium (TBA) salt of FP or phosphatidic acid (DPPA·Na) as templates in combination with a polymerizable nitrobenzoxadiazole (NBD)-urea monomer with the dual role of capturing the phospho-anion and signalling its presence. The monomers were grafted from ca 300 nm RAFT-modified silica core particles using ethyleneglycol dimethacrylate (EGDMA) as crosslinker resulting in 10–20 nm thick shells displaying selective fluorescence response to the targeted lipids S1P and DPPA in aqueous buffered media. Potential use of the sensory particles for monitoring S1P in serum was demonstrated on spiked serum samples, proving a linear range of 18–60 µM and a detection limit of 5.6 µM, a value in the same range as the plasma concentration of the biomarker.