Leiden Institute of Chemistry , Leiden University , P.O. Box 9502, 2300 RA Leiden , The Netherlands.
Van't Hoff Institute for Molecular Sciences , University of Amsterdam , P.O. Box 94157, 1090 GD Amsterdam , The Netherlands.
Langmuir. 2019 Sep 17;35(37):12079-12090. doi: 10.1021/acs.langmuir.9b01318. Epub 2019 Sep 3.
The biological application of ruthenium anticancer prodrugs for photodynamic therapy (PDT) and photoactivated chemotherapy (PACT) is restricted by the need to use poorly penetrating high-energy photons for their activation, i.e., typically blue or green light. Upconverting nanoparticles (UCNPs), which produce high-energy light under near-infrared (NIR) excitation, may solve this issue, provided that the coupling between the UCNP surface and the Ru prodrug is optimized to produce stable nanoconjugates with efficient energy transfer from the UCNP to the ruthenium complex. Herein, we report on the synthesis and photochemistry of the two structurally related ruthenium(II) polypyridyl complexes Ru(bpy)() () and Ru(bpy)() (), where bpy = 2,2-bipyridine, is 5,6-bis(dodecyloxy)-2,9-dimethyl-1,10-phenanthroline, and is 5,6-bis(dodecyloxy)-1,10-phenanthroline. is photolabile as a result of the steric strain induced by ligand , but the irradiation of in solution leads to the nonselective and slow photosubstitution of one of its three ligands, making it a poor PACT compound. On the other hand, is an efficient and photostable PDT photosensitizer. The water-dispersible, negatively charged nanoconjugate UCNP@lipid/[] was prepared by the encapsulation of 44 nm diameter NaYF:Yb,Tm UCNPs in a mixture of 1,2-dioleoyl--glycero-3-phosphate and 1,2-dioleoyl--glycero-3-phosphocholine phospholipids, cholesterol, and the amphiphilic complex . A nonradiative energy transfer efficiency of 12% between the Tm ions in the UCNP and the Ru acceptor [] was found using time-resolved emission spectroscopy. Under irradiation with NIR light (969 nm), UCNP@lipid/[] was found to produce reactive oxygen species (ROS), as judged by the oxidation of the nonspecific ROS probe 2',7'-dichlorodihydrofluorescein (DCFH). Determination of the type of ROS produced was precluded by the negative surface charge of the nanoconjugate, which resulted in the electrostatic repulsion of the more specific but also negatively charged O probe tetrasodium 9,10-anthracenediyl-bis(methylene)dimalonate (Na(ADMBMA)).
钌类抗癌前药在光动力疗法（PDT）和光激活化疗（PACT）中的生物应用受到其激活所需的低穿透力高能光子的限制，即通常是蓝光或绿光。上转换纳米粒子（UCNPs）在近红外（NIR）激发下产生高能光，可能解决这个问题，前提是优化 UCNP 表面与 Ru 前药的偶联，以产生稳定的纳米缀合物，实现高效的能量从 UCNP 转移到钌配合物。在此，我们报告了两种结构相关的钌（II）聚吡啶配合物Ru(bpy)()())和Ru(bpy)()())的合成和光化学性质，其中 bpy=2,2-联吡啶， 是 5,6-双（十二烷氧基）-2,9-二甲基-1,10-菲咯啉， 是 5,6-双（十二烷氧基）-1,10-菲咯啉。由于配体 诱导的空间位阻而具有光解性，但在溶液中辐照会导致其三个配体之一的非选择性和缓慢光取代，使其成为一种较差的 PACT 化合物。另一方面，是一种高效且稳定的 PDT 光敏剂。通过将 44nm 直径的 NaYF:Yb,Tm UCNP 封装在 1,2-二油酰基-sn-甘油-3-磷酸和 1,2-二油酰基-sn-甘油-3-磷酸胆碱磷脂、胆固醇和两亲性配合物的混合物中，制备了带负电荷的水溶性纳米复合物 UCNP@lipid/[]。使用时间分辨发射光谱发现，UCNP 中的 Tm 离子与 Ru 受体[]之间存在 12%的非辐射能量转移效率。在近红外光（969nm）照射下，通过氧化非特异性 ROS 探针 2',7'-二氯二氢荧光素（DCFH），发现 UCNP@lipid/[]能够产生活性氧物种（ROS）。由于纳米复合物的负表面电荷，产生的 ROS 类型的测定受到阻碍，这导致更具特异性但也带负电荷的 O 探针四钠 9,10-蒽二基-双（亚甲基）二马来酸酯（Na(ADMBMA)）发生静电排斥。
