A photodynamic and photochemotherapeutic platinum-iridium charge-transfer conjugate for anticancer therapy

DOI: 10.1002/anie.202400476

Authors: Huayun Shi (University of Warwick) , Oliver W. L. Carter (University of Warwick) , Fortuna Ponte (University of Calabria) , Cinzia Imberti (University of Warwick) , Miguel A. Gomez-Gonzalez (Diamond Light Source) , Fernando Cacho-Nerin (Diamond Light Source) , Paul D. Quinn (Diamond Light Source) , Julia E. Parker (Diamond Light Source) , Emilia Sicilia (University of Calabria) , Huaiyi Huang (University of Warwick; Sun Yat-sen University) , Peter J. Sadler (University of Warwick)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Angewandte Chemie International Edition , VOL 12

State: Published (Approved)
Published: April 2024
Diamond Proposal Number(s): 27852

Abstract: The novel hetero-dinuclear complex trans,trans,trans-[PtIV(py)2(N3)2(OH)(μ-OOCCH2CH2CONHCH2-bpyMe)IrIII(ppy)2]Cl (Pt-Ir), exhibits charge transfer between the acceptor photochemotherapeutic Pt(IV) (Pt-OH) and donor photodynamic Ir(III) (Ir-NH2) fragments. It is stable in the dark, but undergoes photodecomposition more rapidly than the Pt(IV) parent complex (Pt-OH) to generate Pt(II) species, an azidyl radical and 1O2. The Ir(III)* excited state, formed after irradiation, can oxidise NADH to NAD⋅ radicals and NAD+. Pt-Ir is highly photocytotoxic towards cancer cells with a high photocytotoxicity index upon irradiation with blue light (465 nm, 4.8 mW/cm2), even with short light-exposure times (10–60 min). In contrast, the mononuclear Pt-OH and Ir-NH2 subunits and their simple mixture are much less potent. Cellular Pt accumulation was higher for Pt-Ir compared to Pt-OH. Irradiation of Pt-Ir in cancer cells damages nuclei and releases chromosomes. Synchrotron-XRF revealed ca. 4× higher levels of intracellular platinum compared to iridium in Pt-Ir treated cells under dark conditions. Luminescent Pt-Ir distributes over the whole cell and generates ROS and 1O2 within 1 h of irradiation. Iridium localises strongly in small compartments, suggestive of complex cleavage and excretion via recycling vesicles (e.g. lysosomes). The combination of PDT and PACT motifs in one molecule, provides Pt-Ir with a novel strategy for multimodal phototherapy.

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


Instruments: I14-Hard X-ray Nanoprobe

Added On: 29/04/2024 08:54

Documents:
Angew Chem Int Ed - 2024 - Shi - A Photodynamic and Photochemotherapeutic Platinum%E2%80%90Iridium Charge%E2%80%90Transfer Conjugate for.pdf

Discipline Tags:

Non-Communicable Diseases Molecular Complexes Health & Wellbeing Cancer Biochemistry Chemistry Inorganic Chemistry Drug Discovery Life Sciences & Biotech

Technical Tags:

Imaging Spectroscopy X-ray Fluorescence (XRF) X-ray Absorption Spectroscopy (XAS) X-ray Absorption Near Edge Structure (XANES)