Leiden Institute of Chemistry, Leiden University, P.O. Box 9502, 2300 RA, Leiden, The Netherlands.
Institute of Condensed Matter Chemistry and Technologies for Energy, National Research Council (CNR), Department of Chemical Sciences, University of Padova, via F. Marzolo 1, 35131 Padova, Italy.
Inorg Chem. 2020 Oct 19;59(20):14807-14818. doi: 10.1021/acs.inorgchem.0c00043. Epub 2020 Mar 13.
The biological application of photoactivatable ruthenium anticancer prodrugs is limited by the need to use poorly penetrating high-energy visible light for their activation. Upconverting nanoparticles (UCNPs), which produce high-energy light under near-infrared (NIR) excitation, can solve this issue, provided that they form stable, water (HO)-dispersible nanoconjugates with the prodrug and that there is efficient energy transfer from the UCNP to the ruthenium complex. Herein, we report on the synthesis and photochemistry of the ruthenium(II) polypyridyl complex Ru(bpy)() (), where bpy = 2,2-bipyridine and is a photocleavable bis(thioether) ligand modified with two phosphonate moieties. This ligand was coordinated to the ruthenium center through its thioether groups and could be dissociated under blue-light irradiation. Complex was bound to the surface of NaYF:Yb,Tm@NaYF:Nd@NaYF core-shell-shell (CSS-)UCNPs through its bis(phosphonate) group, thereby creating a HO-dispersible, thermally stable nanoconjugate (CSS-UCNP@[]). Conjugation to the nanoparticle surface was found to be most efficient in neutral to slightly basic conditions, resulting in up to 2.4 × 10 Ru ions per UCNP. The incorporation of a neodymium-doped shell layer allowed for the generation of blue light using low-energy, deep-penetrating light (796 nm). This wavelength prevents the undesired heating seen with conventional UCNPs activated at 980 nm. Irradiation of CSS-UCNP@[] with NIR light led to activation of the ruthenium complex . Although only one of the two thioether groups was dissociated under irradiation at 50 W·cm, we provide the first demonstration of the photoactivation of a ruthenium thioether complex using 796 nm irradiation of a HO-dispersible nanoconjugate.
光激活钌类抗癌前药的生物应用受到需要使用穿透力差的高能可见光进行激活的限制。上转换纳米粒子（UCNP）在近红外（NIR）激发下产生高能光，可以解决这个问题，只要它们与前药形成稳定的、可在水中（HO）分散的纳米复合物，并且 UCNP 向钌配合物有效转移能量。在此，我们报告了钌（II）多吡啶配合物 Ru(bpy)() () 的合成和光化学性质，其中 bpy = 2,2-联吡啶， 是一个带有两个膦酸酯部分的光解双硫醚配体。该配体通过其硫醚基团与钌中心配位，并在蓝光照射下可发生解离。配合物 通过其双膦酸酯基团结合到 NaYF:Yb,Tm@NaYF:Nd@NaYF 核壳壳（CSS-）UCNP 的表面，从而形成 HO 可分散、热稳定的纳米复合物（CSS-UCNP@[]）。在中性到稍碱性条件下，发现与纳米粒子表面的键合最有效，导致每个 UCNP 上有多达 2.4×10 的 Ru 离子。掺入掺杂有钕的壳层允许使用低能量、深穿透光（796nm）产生蓝光。这种波长可以防止使用在 980nm 处激活的常规 UCNP 产生的不必要加热。用 NIR 光照射 CSS-UCNP@[]导致钌配合物 的激活。尽管在 50 W·cm 的照射下只有一个硫醚基团发生解离，但我们首次证明了使用 HO 可分散纳米复合物在 796nm 照射下对钌硫醚配合物的光激活。
