Annual Review 2024-2025

D I A M O N D L I G H T S O U R C E L I M I T E D 25 sensitivity vibrational spectroscopy in Fourier Transform IR (FTIR) mode, plus TeraHertz (THz) spectroscopy. Since 2022, a nanoIR endstation couples an Atomic Force Microscope to the B22 beamline and uniquely measures photothermal (AFM IR) and scattering (s-SNOM) nanospectroscopy at sub-wavelength resolution. B23 is a life sciences, chemistry and material science beamline for investigating and observing structural, functional and dynamic interactions in proteins, nucleic acids, nanoparticles and polymers using UV-CD. B23 is a world-leading instrument in Muller Matrix polarimetry for studying chiral materials which can detect the emergence of chirality from achiral particles. Unveiling the subcellular impact of metallo-drugs by infrared nanospectroscopy New treatments are urgently required for osteosarcoma, a type of cancer that mainly occurs in children and teenagers. Current treatments mostly rely on DNA-damaging agents such as cisplatin, which was the first platinum-based anti-cancer metallodrug, introduced in the clinics in the 1970s. However, the in vivo anticancer activity of cisplatin is severely limited by low bioavailability, serious side effects and acquired resistance. Researchers from the University of Coimbra in Portugal carried out synchrotron nano-FTIR measurements on cisplatin-exposed human osteosarcoma cells as well as on drug-free (control) cells. This method allows topography, mechanical response and optical images to be obtained simultaneously, in this case revealing a high sub-cellular heterogeneity at the nanometre scale. The data show well resolved cell topography and organelle contours, and the nano-FTIR spectra revealed the impact of cisplatin on cellular proteins, lipids and DNA. The new information gathered during these experiments adds to data previously obtained on different scales using micro-FTIR and THz spectroscopies, together with micro-Raman and neutron scattering methods (both inelastic and quasi-elastic). By adding subcellular-level insight on the effect of the drug on specific cellular regions and biochemical components, it goes a step further, demonstrating the potential for using synchrotron nano-FTIR as a suitable nanospectroscopy probe in biomedical research. This new approach to studying the mode of action of metallodrugs at a molecular and subcellular level will be a key tool in the development of improved anticancer agents, potentially leading to improved clinical outcomes and a better quality of life for oncology patients. DOI:10.1038/s41598-024-67386-y S O F T C O N D E N S E D M AT T E R G R O U P Synchrotron-radiation nano-FTIR spectra, for human osteosarcoma cells (MG-63, formalin-fixed) both untreated and treated with cisplatin, averaged over all the points of the line-scans shown in corresponding top graphic images (inset). Wavelength (cm-1) Untreated Treated Amplitude (A.U.)