66 67 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 Directing lipid nanoparticles for anticancer therapy Drug Delivery – Non-Communicable Diseases – Health &Wellbeing – Cancer – Materials Science – Nanoscience/Nanotechnology – Life Sciences & Biotech Nanomedicine is a rapidly growing field that uses nanoparticles to diagnose and treat diseases. Nanoparticles are tiny particles smaller than 100 nanometres, about 1/1000th the width of a human hair. Nanoparticle formulations can be made from a variety of materials, including proteins, polymers, lipids, metals, and inorganic elements. The advantages of using nanoparticles over traditional drugs and therapies include targeting treatments to specific cells or tissues, which can improve the effectiveness of treatment and reduce the risk of side effects. Nanoparticles can also deliver drugs or other therapies to areas of the body that are difficult to reach with traditional methods. Lipid nanoparticles (LNPs) have attracted enormous interest as drug delivery vehicles; for example, LNPs were essential to the development of COVID-19 mRNA vaccines. 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 havemainly been used for passive targeting, which often leads to off-target toxicity. Their cytotoxicity and biodistribution in vivo are largely underexplored, hindering clinical translation. Researchers from the University of Leeds attached a synthetic antibody, known as an Affimer, to the surface of engineered cubosomes that were loaded with a model chemotherapeutic drug to actively target colorectal cancer cells. They used a range of biophysical techniques to characterise the cubosomes and studied their therapeutic efficacy extensively in colorectal cancer models both in vitro (2D cell culture and 3D spheroid models) and in vivo in tumour xenograft bearing mice. After collecting preliminary Small Angle X-ray Scattering (SAXS) data on the Diamond-Leeds offline SAXS instrument (DL-SAXS), the team used Diamond’s I22 beamline to characterise the internal nanostructure adopted by the LNPs upon surface functionalisation and drug encapsulation. Using SAXS was essential, as the internal nanostructure strongly correlates to their in vivo performance and greatly impacts the LNPs formation-structure-function relationship. The high flux, tuneable energy and spatial/temporal resolution on I22 were crucial, giving diffraction patterns from the weakly scattering dilute samples and resolving the Bragg reflections expected. 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 invitro and invivo ,whilst showing lownon-specific absorptionand 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. Understanding how the nanostructure of LNPs leads to function is key to their successful clinical translation. This work focused on engineering LNPs for colorectal cancer treatment. However, understanding LNP structure-function relationships is essential for the development of novel drug delivery vehicles to target a multitude of diseases, vaccines and gene therapy. Related publication: Pramanik, A. et al. Affimer tagged cubosomes: Targeting of carcinoembryonic antigen expressing colorectal cancer cells using in vitro and in vivo models. ACS Applied Materials & Interfaces 14 , 11078-11091 (2022). DOI: 10.1021/acsami.1c21655 Funding acknowledgement: Newton Postdoctoral Fellowship awarded to Arindam Pramanik (grant no. NIF003\1007) University of Leeds (start-up funding, PhD scholarship) EPSRC (grant no. EP/R042683/1) Corresponding authors: Thomas A. Hughes, University of Leeds,
[email protected] Arwen I. I. Tyler, University of Leeds,
[email protected] Soft CondensedMatter Group Beamline I22 and the DL-SAXS Instrument Engineered lipid nanoparticles (cubosomes), loaded with the drug copper acetylacetonate (blue), and with their surfaces functionalized with Affimers that bind carcinoembryonic antigen (red). This potential nanomedicine binds specifically to colorectal cancer cells, restricting tumour growth. Capturing Sulphur-dioxide in Zirconium-basedMetal-Organic Frameworks Desertification & Pollution – Earth Sciences & Environment – Chemistry – Materials Science – Chemical Engineering – Engineering & Technology – Metal-Organic Frameworks – Metallurgy – Organometallic Chemistry The growing concern over air pollution has driven the search for new and efficient methods to remove industrial emissions, and desirably to enable recovery from exhaust gases with conversion into chemical feedstocks. Sulphur-dioxide (SO 2 ) is a major air pollutant with a significant impact on human health. Its highly corrosive and reactive nature generally leads to severe structural degradation in capture materials. Metal-organic frameworks (MOFs) are porous, crystalline-like materials, and Zirconium-based metal-organic frameworks (Zr-MOFs) have emerged as promising materials for exhaust gases’ capture due to their high surface area and tuneable pore environment. Therefore, understanding the interactions between e.g. SO 2 and the pore environment of Zr-MOFs is essential to designing efficient and stable materials for Sulphur-dioxide capture. By studying the pore environment and its impact on SO 2 adsorption, researchers can develop new principles for the design of MOFs with high Sulphur- dioxide adsorption at both low and high concentrations, enabling their use in a broader range of applications and contributing to the mitigation of air pollution. In addition, the development of regenerable methods for SO 2 capture and recycling of the sorbent material can also reduce waste production and support the sustainability of the technology. The porous nature of MOFs allows them to capture guest molecules, and host-guest interactions are of fundamental importance. Researchers from the University of Manchester in collaboration with Diamond beamline B22 scientists used a combination of infrared micro-spectroscopy (microFTIR) on Diamond’s B22 beamline and in situ X-ray diffraction on I11, together with inelastic neutron scattering at the ISIS Neutron & Muon Source to enable the visualisation of the binding domains of adsorbed SO 2 molecules and host-guest binding dynamics in Zr-MOFs at the atomic scale and molecular level. Their results demonstrated that introducing functional groups (i.e . -NH 2 and –S-) and atomically-dispersed Cu II sites into a family of Zr-MOFs can effectively enhance the adsorption of Sulphur- dioxide at low pressure. In addition, the confined metal-ligand cages in Zr-bptc offer an optimal pore environment for effective SO 2 capture and conversion. Revealing the role of the pore environment (including pore size, pore geometry and functional groups) and understanding the fundamental host- guest chemistry at the atomic and molecular level making a revolutionary change to the design of the next generation of functional materials. This work will inform the design of new materials optimised for Sulphur- dioxide capture. These could be applied to storage systems to minimise transport costs and space. In addition, materials with exceptional Sulphur- dioxide capture capability at low pressure will incubate the development of in-vehicle desulphurisation devices. Related publication: Li, J. et al. Structural and dynamic analysis of Sulphur- dioxide adsorption in a series of Zirconium-based Metal-Organic Frameworks. Angewandte Chemie International Edition 61, 36: e202207259 (2022). DOI:10.1002/ anie.202207259 Funding acknowledgement: EPSRC, grant number EP/I011870 ERC, grant agreement No 742401, NANOCHEM DLS-Manchester University, Meredydd Kippax-Jones co-funded PhD studentship Corresponding authors: Martin Schröder, Department of Chemistry, University of Manchester,
[email protected] Sihai Yang, Department of Chemistry, University of Manchester
[email protected] Soft CondensedMatter Group Beamline B22 (and I11 from the Crystallography Group) IR spectra of (i) ν(μ3-OH) and (ii) ν(S−C) stretching region for Zr-DMTDC at various loadings of SO 2 ; (iii). Views of corresponding structures (in various SO 2 -loading experiments: black: bare MOF, red: 1% SO 2 -loading, blue: 2% SO 2 -loading, green: 5% SO 2 -loading, violet: 10% SO 2 -loading, dark yellow: 20% SO 2 -loading, cyan: 40% SO 2 -loading, light wine: 60% SO 2 -loading, wine: 80% SO 2 -loading, orange: 100% SO 2 -loading).