In-cell synchrotron investigations of precious-metal anticancer complexes

Authors: Elizabeth M. Bolitho (University of Warwick)
Co-authored by industrial partner: No

Type: Thesis

State: Published (Approved)
Published: June 2020

Abstract: latinum (II) anticancer drugs are used in over 50% of all chemotherapeutic treatments worldwide, however, platinum-resistance is a major clinical concern. Platinum-group complexes are of significant interest in the development of anticancer drugs which overcome such resistance, with improved selectivity for cancer vs. healthy cells, ultimately enhancing the drug efficacy and reducing patient side effects. In this thesis, three families of metal complexes have been investigated: (i) OsII half-sandwich complexes for catalytic therapy, (ii) cyclometallated IrIII complexes for photodynamic therapy (PDT) and (iii) diazido-PtIV prodrugs for photoactivatable chemotherapy (PACT). Determination of the chemical speciation of such complexes in cancer cells is essential for understanding the antiproliferative mechanisms of action. Herein, the speciation, distribution and stability of such complexes in cancer cells have been probed using Inductively-Coupled Plasma Mass Spectrometry (ICP-MS), synchrotron X-ray Fluorescence (XRF), Differential Phase Contrast (DPC) imaging and synchrotron X-ray Absorption Near Edge Structure (XANES) spectroscopy. Complementary to this, cryogenic fluorescence microscopy, Structured Illumination Microscopy (SIM) and synchrotron soft X-ray Tomography (XRT) have been used to investigate the 3D drug distribution and morphological changes in cancer cells down to a subcellular resolution (40 nm).

Subject Areas: Biology and Bio-materials, Chemistry, Medicine


Instruments: B24-Cryo Soft X-ray Tomography , I14-Hard X-ray Nanoprobe

Added On: 21/08/2024 12:06

Discipline Tags:

Non-Communicable Diseases Health & Wellbeing Cancer Biochemistry Chemistry Structural biology Drug Discovery Life Sciences & Biotech

Technical Tags:

Imaging Microscopy Spectroscopy Tomography X-ray Fluorescence (XRF) X-ray Microscopy Cryo X-ray Microscopy X-ray Absorption Spectroscopy (XAS) X-ray Absorption Near Edge Structure (XANES) Cryo-soft X-ray Tomography (Cryo-SXT) CryoSIM