具有“聚集诱导发光”性质的纳米材料的制备及其生物医学应用
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摘要
肿瘤酸性微环境(pH 6.8-7.2)已经被广泛报道。此外,具有"聚集诱导发光(AIE)"性质的荧光分子是一种新型的荧光材料,目前已经被广泛应用于生物传感与生物成像[1]。AIE荧光分子在单分子状态下几乎是不发荧光的,但是在聚集状态下由于分子内转子的旋转受限而发射很强的荧光,利用这一性质,我们采用AIE荧光分子来构筑纳米荧光探针用于响应肿瘤组织微酸性的环境。我们将典型的AIE荧光分子(tetraphenylsilole;TPS)共价连接到带正电荷的高分子polyethyleneimine(PEI)上,然后将PEI上的氨基与2,3-dimethylmaleic anhydride(DMA)反应,得到带较强负电荷的纳米探针(TPS-PEI-DMA)。由于DMA上的双键能够淬灭TPS的荧光,带负电荷的TPS-PEI-DMA纳米探针是不发荧光的。在肿瘤酸性微环境下,DMA与PEI间的酰胺键断裂,纳米探针的表面电荷转变为正,有利于大量地进入肿瘤细胞并且选择性地抑制肿瘤细胞的生长。此外,由于DMA的离去,纳米探针的荧光恢复,能够选择性地照亮肿瘤细胞。我们制备的肿瘤酸性微环境响应的AIE纳米探针能够用于肿瘤细胞成像和选择性地抑制肿瘤细胞[2]。
It is well established that the pH value in tumor extracellular environment(p He) is slightly acidic(6.8-7.2). Additionally, a novel class of organic fluorogens with unique aggregation-induced emission(AIE) feature has been widely used for biosensing and bioimaging applications. We covalently conjugated both AIE fluorophore(tetraphenylsilole; TPS) and 2,3-dimethylmaleic anhydride(DMA) to the polyethyleneimine(PEI), affording negatively charged nanoparticle probe TPS-PEI-DMA. The nanoparticle probe is almost non-fluorescent and carrying negatively charges in physiological conditions. In acidic condition, the surface charges of TPS-PEI-DMA switch to positive, which endow the nanoparticle probe with the abilities to be internalized into the cancer cells as well as significantly turn on its fluorescence. It is also demonstrated that TPS-PEI-DMA can significantly light up the cancer cells. The cytotoxicity results also reveal that TPS-PEI-DMA shows low cytotoxicity to normal cells and relatively high cytotoxicity to cancer cells.
引文
[1]Ding,D.;Li,K.;Liu,B.;Tang,B.Z.Acc.Chem.Res.2013,46:2441.
    [2]Ding,D.;Kwok.R.T.K.;Yuan,Y.;Feng,G.;Tang,B.Z.;Liu,B.Mater.Horiz.2015,2:100.

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