Department of Materials Science and Technology , Nagaoka University of Technology , Kamitomioka 1603-1 , Nagaoka , Niigata 940-2188 , Japan.
Graduate School of Dental Medicine , Hokkaido University , Sapporo 060-8586 , Japan.
ACS Appl Mater Interfaces. 2019 Mar 6;11(9):8915-8927. doi: 10.1021/acsami.8b22740. Epub 2019 Feb 20.
We synthesized hydroxyapatite nanocrystals under the existence of tris(2,2,6,6-tetramethyl-3,5-heptanedionato)europium(III) (EuTH) complex to form inorganic/organic hybrid nanocrystal (EHA). Then, the folic acid derivative (folate N-hydroxysuccinimidyl ester (FA-NHS)) as the targeting ligand for the HeLa cancer cells was immobilized on the EHA by the mediation of both 3-aminopropyltriethoxysilane and methyltriethoxysilane molecules. Here, we investigated the photofunctions based on the interfacial interactions between the FA-NHS and EHA nanohybrids for preparing the novel bioimaging nanomaterials. As a result, the photofunctions could be changed by the FA-NHS molecular occupancy on the EHA. When the molecular occupancy ratio to the EHA surfaces is at around 3-5%, the intense luminescence from the f-f transition of the Eu ions as well as the charge transfer between the EuTH-FA-NHS was observed to exhibit higher quantum efficiency. Moreover, effective dispersibility in phosphate-buffered saline was confirmed with immobilizing the positively charged FA-NHS. The cytotoxicity against the HeLa cells was also evaluated to verify whether the nanohybrids can be the candidate for cell imaging. The affinity and noncytotoxicity between the FA-NHS-immobilized EHA nanohybrids and cells were monitored for 3 days. Red luminescence from the cells could be observed, and the labels with following the cellular shapes were achieved by an additional culture time of 1 h after injecting the FA-NHS-immobilized EHA nanohybrids to the spheres, indicating the rapid bioimaging process. Therefore, this is the first successful report to describe the synthesis of inorganic-organic nanohybrid systems for controlling the EuTH-FA-NHS interactions. The photofunction of the interfacial interactions was successfully designed to provide "efficient luminescent ability" as well as "rapid targeting to the cancer cells" in one particle.
我们在三（2,2,6,6-四甲基-3,5-庚二酮）铕（III）（EuTH）配合物的存在下合成了羟基磷灰石纳米晶体，形成了无机/有机杂化纳米晶体（EHA）。然后，叶酸衍生物（叶酸 N-羟基琥珀酰亚胺酯（FA-NHS））作为靶向配体通过 3-氨丙基三乙氧基硅烷和甲基三乙氧基硅烷分子固定在 EHA 上。在这里，我们研究了基于 FA-NHS 和 EHA 纳米杂化物界面相互作用的光功能，以制备新型生物成像纳米材料。结果，光功能可以通过 FA-NHS 分子在 EHA 上的占据来改变。当分子占据率约为 EHA 表面的 3-5%时，观察到 Eu 离子的 f-f 跃迁的强烈发光以及 EuTH-FA-NHS 之间的电荷转移表现出更高的量子效率。此外，通过固定带正电荷的 FA-NHS 证实了在磷酸盐缓冲盐水中的有效分散性。还评估了对 HeLa 细胞的细胞毒性，以验证纳米杂化物是否可以成为细胞成像的候选物。监测了 FA-NHS 固定化 EHA 纳米杂化物与细胞之间的亲和力和非细胞毒性 3 天。可以观察到来自细胞的红色发光，并且在将 FA-NHS 固定化的 EHA 纳米杂化物注入球体后再培养 1 小时，实现了与细胞形状相匹配的标记，表明快速的生物成像过程。因此，这是第一个成功的报告，描述了用于控制 EuTH-FA-NHS 相互作用的无机-有机纳米杂化系统的合成。成功地设计了界面相互作用的光功能，以提供“高效发光能力”以及“快速靶向癌细胞”。
