School of Chemistry, University of Birmingham, Edgbaston, B15 2TT, UK.
Dept. of Surgical Biotechnology, Faculty of Medical Sciences, University College London, London, UK.
Nanoscale. 2024 Sep 12;16(35):16500-16509. doi: 10.1039/d4nr01901f.
Osmium(II) complexes have attractive properties for potential theranostic agents given their anticancer activitiy, their redox potentials favourable for biological transformations within cancer cells and their luminescence in the near infrared (NIR) region. To achieve localised detection and delivery, gold nanoparticles (AuNP) provide an attractive scaffold to attach multiple luminescent agents on a single particle and provide a multimodal platform for detection and loaclaised delivery. We have developed 13 nm and 25 nm AuNP decorated with an osmium complex based on 1,10-phenantholine and surface active bipyridine ligands, OsPhenSS for live cell imaging and singlet oxygen generation, notated as OsPhenSS·AuNP13 and OsPhenSS·AuNP25. The AuNP designs not only allow versatile modalities for localisation of the probe but also water solubility for the osmium metal complex. The osmium decorated nanoparticles OsPhenSS·AuNP13 and OsPhenSS·AuNP25 display characteristic NIR luminescence from the osmium(II) MLCT at 785 nm in aqueous solutions with visible excitation. Upon incubation of the nanoparticles in lung cancer and breast carcinoma the luminescence signature of osmium and the gold reflectance reveal localisation in the cytoplasmic and perinuclear compartments. Excitation of the nanoparticles at 552 nm in the presence of a ROS indicator revealed a marked increase in the green fluorescence from the indicator, consistent with photo-induced ROS generation. The detection of singlet oxygen by time-resolved luminescence studies of the osmium and the nanoparticle probes further demonstrates the dual activity of the osmium-based nanoprobes for imaging and therapy. The introduction of gold nanoparticles for carrying osmium imaging probes allows a novel versatile strategy combining detection and localised therapies at the nanoscale.
锇（II）配合物具有抗癌活性、在癌细胞内进行生物转化的氧化还原电位有利以及在近红外（NIR）区域发光等吸引人的特性，因此非常适合作为潜在的治疗诊断试剂。为了实现局部检测和递药，金纳米粒子（AuNP）为附着多个发光剂提供了一个有吸引力的支架，并为检测和局部递药提供了一个多模态平台。我们开发了基于 1,10-菲咯啉和表面活性联吡啶配体的 13nm 和 25nmAuNP 上修饰的锇配合物 OsPhenSS，用于活细胞成像和单线态氧生成，分别标记为 OsPhenSS·AuNP13 和 OsPhenSS·AuNP25。AuNP 设计不仅允许灵活的定位方式，还允许水溶解锇金属配合物。在水溶液中，具有可见激发的 OsPhenSS·AuNP13 和 OsPhenSS·AuNP25 纳米粒子显示出特征性的近红外发光，来自锇（II）MLCT 在 785nm 处。将纳米粒子孵育在肺癌和乳腺癌中时，锇的发光特征和金的反射率显示出在细胞质和核周区的定位。在存在 ROS 指示剂的情况下，用 552nm 激发纳米粒子时，指示剂的绿色荧光明显增加，这与光诱导的 ROS 生成一致。通过时间分辨发光研究对锇和纳米粒子探针的单线态氧检测进一步证明了基于锇的纳米探针在成像和治疗方面的双重活性。金纳米粒子的引入用于携带锇成像探针，为在纳米尺度上结合检测和局部治疗提供了一种新的多功能策略。
