Diamond Light Source - Annual Review 2022/23 - Concise Edition

32 33 D I A M O N D L I G H T S O U R C E A N N U A L R E V I E W 2 0 2 2 / 2 3 D I A M O N D L I G H T S O U R C E A N N U A L R E V I E W 2 0 2 2 / 2 3 Soft CondensedMatter Group T he Soft Condensed Matter (SCM) Group is comprised of four beamlines at Diamond: High Throughput Small Angle X-ray Scattering (SAXS) (B21), Multimode Infrared Imaging and Microspectroscopy (MIRIAM) (B22), SAXS and Diffraction (I22) and Circular Dichroism Microspectroscopy (B23). This unique portfolio of instruments enables studies of non-crystalline materials at nano- to meso-scale resolutions that include two-dimensional thin-films (photovoltaics, OLEDs), livingmammaliancells, three-dimensionalmatrices (metalorganic frameworks, gels, andwaxes) and nanoparticles in non-crystalline states. SCM science is “the science that underpins continued improvements to quality of life”. The SCMuser community is international, with nearly 70%of our peer reviewed allocated beamtime to UK users with the remain- ing time shared between other international users. Studies this year focused on nanomaterials development as new treatments. Functionalised cubic phase nanoparticles Focused delivery of chemotherapy drugs at tumour sites can increase the effectiveness of the treatments while reducing potential side effects. This long- standing challenge is being addressed using next-generation nanostructured liquid crystalline nanoparticles (NPs) called cubosomes. Cubosomes have high loading capacity, biocompatibility and thermostability, and have been shown to effectively deliver therapeutics to tumour sites in the patient’s body. Researchers evaluated an active tumour targeting cubosome system directed towards rhabdomyosarcoma (RMS) cells. They employed a top-down synthesis approach to produce blank cubic phase NPs, which were subsequently functionalised with hyaluronic acid (HA), anti-CD221 half-sized antibodies (ha- Abs) and superparamagnetic iron oxide nanoparticles (SPIONs). They used Small-Angle X-ray Scattering (SAXS) measurements on Diamond’s B21 beamline to investigate the lipid lattice patterns and verified the formation of cubic phases. Both SAXS and cryo-Electron Microscopy (cryo-EM) performed at the Electron Bio-Imaging Centre (eBIC) played an important role in optimising the cubosome synthesis method and validating the structures throughout the investigation. The cubosome-based drug delivery platform constructed in this study can encapsulate large quantities of hydrophilic, lipophilic, or amphiphilic therapeutics and confine the chemotherapy to tumour tissues in an active manner. In addition, the cubosome synthesis and functionalisation procedures the team has established may also be useful in structural biology, vaccine, transfection, cosmetics, or biomedical imaging. Mun, H. et al. DOI:10.1007/s12274-022-5037-4 Directing lipid nanoparticles for anticancer therapy Nanomedicine is a rapidly growing field that uses nanoparticles to diagnose and treat diseases. The advantages of using nanoparticles include targeting treatments to specific cells or tissues, which can improve the effectiveness of treatment and reduce the risk of side effects. Lipid nanoparticles (LNPs) have attracted enormous interest as drug delivery vehicles. LNPs with an internal cubic symmetry, termed cubosomes, are an emerging class of nanoparticles that offer several advantages, such as high encapsulation of cargo and biocompatibility. To date, however, cubosomes have mainly been used for passive targeting, which often leads to off-target toxicity. Researchersattachedasyntheticantibody, knownasanAffimer, tothesurface of engineered cubosomes that were loadedwith amodel chemotherapeutic drug to actively target colorectal cancer cells. The teamused Diamond’s I22 beamline and the Diamond-Leeds offline SAXS instrument (DL-SAXS) to characterise the internal nanostructure adopted by the LNPs upon surface functionalisation and drug encapsulation. The results showed that surface functionalisation and drug encapsulation didn’t alter the internal nanostructure symmetry of the LNPs. The cubosomes exhibited preferential accumulation in cancer cells compared to normal cells both in vitro and in vivo , whilst showing low non-specific absorption and toxicity in other vital organs. Mice subjected to targeted drug-loaded cubosomes experienced: increased drug accumulation in the tumour tissue compared to other vital organs, a decrease in tumour growth, and increased survival rates compared to control groups, demonstrating the exciting potential for Affimer- tagged cubosomes in therapeutic applications. Pramanik, A. et al. DOI: 10.1021/acsami.1c21655 Fine-tuning poly-L-lysine-based antiviral nanomaterials The appearance of new and lethal viruses requires innovative antiviral systems. Nanomaterials can represent alternative resources to fight viruses at different stages of infection by selective action or in a broad spectrum. A fundamental requirement is non-toxicity. However, biocompatible nanomaterials often have little or no antiviral activity, preventing their practical use. Carbon- based nanomaterials have displayed encouraging results and can present the required mix of biocompatibility and antiviral properties. Researchers recently synthesised a polymeric nanomaterial, derived fromthe amino acid L-lysine, with an antiviral activity against SARS-CoV-2 and a good safety profile in vitro. The research group is developing a new generation of lysine-based nanostructures by modifying the lysine branched structure with other amino acids, such as arginine and glycine, whose structure is not yet understood. They used Synchrotron Radiation Circular Dichroism (SRCD) on Diamond’s B23 beamline to understand the supramolecular structure of this peculiar class of biomaterials. The structural analysis of the poly-L-lysine (PLL) obtained after a hydrothermal treatment (HT) at 200 °C of L-lysine showed significant differences in the homopeptide architecture as a function of pH. It is, therefore, possible to tune the synthesis process to obtain cross-linked or linear lysine polymers by modulating the pH of the starting solution. The knowledge acquired in this study has enabled the design of very specific L-lysine- based nanosystems that can inhibit the replication of different types of viruses with potential broad-spectrum responses. Stagi, L. et al. DOI: 10.1038/s41598-022-24109-5 Experimental Michelson Interferometer setup, part of the infrared nanoscope on beamline B22.