Near infra-red luminescent osmium labelled gold nanoparticles for cellular imaging and singlet oxygen generation.

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) 3MLCT 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.

Supramolecular Cylinders Target Bulge Structures in the 5' UTR of the RNA Genome of SARS-CoV-2 and Inhibit Viral Replication.

The untranslated regions (UTRs) of viral genomes contain a variety of conserved yet dynamic structures crucial for viral replication, providing drug targets for the development of broad spectrum anti-virals. We combine in vitro RNA analysis with molecular dynamics simulations to build the first 3D models of the structure and dynamics of key regions of the 5' UTR of the SARS-CoV-2 genome. Furthermore, we determine the binding of metallo-supramolecular helicates (cylinders) to this RNA structure. These nano-size agents are uniquely able to thread through RNA junctions and we identify their binding to a 3-base bulge and the central cross 4-way junction located in stem loop 5. Finally, we show these RNA-binding cylinders suppress SARS-CoV-2 replication, highlighting their potential as novel anti-viral agents.