TY - JOUR
T1 - A Photodynamic and Photochemotherapeutic Platinum-Iridium Charge-Transfer Conjugate for Anticancer Therapy
AU - Shi, Huayun
AU - Carter, Oliver W.L.
AU - Ponte, Fortuna
AU - Imberti, Cinzia
AU - Gomez-Gonzalez, Miguel A.
AU - Cacho-Nerin, Fernando
AU - Quinn, Paul D.
AU - Parker, Julia E.
AU - Sicilia, Emilia
AU - Huang, Huaiyi
AU - Sadler, Peter J.
N1 - Publisher Copyright:
© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.
PY - 2024/6/3
Y1 - 2024/6/3
N2 - 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.
AB - 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.
KW - Anticancer
KW - Heterometallic complex
KW - Phototherapy
KW - Synchrotron X-rays
KW - TDDFT
UR - http://www.scopus.com/inward/record.url?scp=85191155563&partnerID=8YFLogxK
U2 - 10.1002/anie.202400476
DO - 10.1002/anie.202400476
M3 - Article
C2 - 38656762
AN - SCOPUS:85191155563
SN - 1433-7851
VL - 63
JO - Angewandte Chemie - International Edition
JF - Angewandte Chemie - International Edition
IS - 23
M1 - e202400476
ER -
