Pt(II)-Phenanthroline-Ln(III)-DOTA d–f Hybrids as Small-Molecule Theranostics

Beatriz Brito; Thomas W. Price; Manuel Bañobre-López; Juan Gallo; Graeme J. Stasiuk

doi:10.1002/ejic.202400063

Pt(II)-Phenanthroline-Ln(III)-DOTA d–f Hybrids as Small-Molecule Theranostics

Beatriz Brito, Thomas W. Price, Manuel Bañobre-López, Juan Gallo, Graeme J. Stasiuk^*

^*Corresponding author for this work

Imaging Chemistry & Biology

Research output: Contribution to journal › Article › peer-review

Abstract

1,10-Phenanthroline d- or f-metal complexes can be utilised in biomedical applications such as imaging or therapeutics. Herein, we designed bimetallic d-block metal-phenanthroline f-block metal-1,4,7,10-tetraazacyclododecane-1,4,7,1,0-tetraacetic acid (DOTA) conjugates as theranostic agents to simultaneously achieve both of these applications. Luminescence studies show the 1,10-phenanthroline-Eu(III)-DOTA complexes displayed an off/on/off pH-dependent switch, demonstrating their potential as pH-responsive lanthanide luminescence probes. Relaxometry studies showed that the 1,10-phenanthroline-Gd(III)-DOTA complexes present a r1 of 5.15±0.05 mM−1 s−1 and could thus be used as magnetic resonance (MR) contrast agents. Complexation of Pt(II) by the 1,10-phenanthroline moiety resulted in quenching of the Eu(III) luminescence, but an enhancement of the Gd(III) relaxivity (r1=7.53±0.69 mM−1 s−1). Cell viability studies of the d–f hybrids in a cancer cell line showed the potential of these complexes as anticancer agents, as the IC50 for the Pt(II)/Gd(III) complex (IC50=24.9 μM) was lower than that of cisplatin (IC50=31.6 μM). As such, Pt(II)-1,10-phenanthroline-Gd(III)-DOTA complexes are promising theranostic agents for cancer therapy.

Original language	English
Article number	e202400063
Journal	EUROPEAN JOURNAL OF INORGANIC CHEMISTRY
Volume	27
Issue number	17
Early online date	21 May 2024
DOIs	https://doi.org/10.1002/ejic.202400063
Publication status	Published - 12 Jun 2024

Keywords

cancer therapy
Magnetic resonance imaging
phenanthroline
platinum
theranostics

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title = "Pt(II)-Phenanthroline-Ln(III)-DOTA d–f Hybrids as Small-Molecule Theranostics",

abstract = "1,10-Phenanthroline d- or f-metal complexes can be utilised in biomedical applications such as imaging or therapeutics. Herein, we designed bimetallic d-block metal-phenanthroline f-block metal-1,4,7,10-tetraazacyclododecane-1,4,7,1,0-tetraacetic acid (DOTA) conjugates as theranostic agents to simultaneously achieve both of these applications. Luminescence studies show the 1,10-phenanthroline-Eu(III)-DOTA complexes displayed an off/on/off pH-dependent switch, demonstrating their potential as pH-responsive lanthanide luminescence probes. Relaxometry studies showed that the 1,10-phenanthroline-Gd(III)-DOTA complexes present a r1 of 5.15±0.05 mM−1 s−1 and could thus be used as magnetic resonance (MR) contrast agents. Complexation of Pt(II) by the 1,10-phenanthroline moiety resulted in quenching of the Eu(III) luminescence, but an enhancement of the Gd(III) relaxivity (r1=7.53±0.69 mM−1 s−1). Cell viability studies of the d–f hybrids in a cancer cell line showed the potential of these complexes as anticancer agents, as the IC50 for the Pt(II)/Gd(III) complex (IC50=24.9 μM) was lower than that of cisplatin (IC50=31.6 μM). As such, Pt(II)-1,10-phenanthroline-Gd(III)-DOTA complexes are promising theranostic agents for cancer therapy.",

keywords = "cancer therapy, Magnetic resonance imaging, phenanthroline, platinum, theranostics",

author = "Beatriz Brito and Price, {Thomas W.} and Manuel Ba{\~n}obre-L{\'o}pez and Juan Gallo and Stasiuk, {Graeme J.}",

note = "Publisher Copyright: {\textcopyright} 2024 The Authors. European Journal of Inorganic Chemistry published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.",

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T1 - Pt(II)-Phenanthroline-Ln(III)-DOTA d–f Hybrids as Small-Molecule Theranostics

AU - Brito, Beatriz

AU - Price, Thomas W.

AU - Bañobre-López, Manuel

AU - Gallo, Juan

AU - Stasiuk, Graeme J.

N1 - Publisher Copyright: © 2024 The Authors. European Journal of Inorganic Chemistry published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

PY - 2024/6/12

Y1 - 2024/6/12

N2 - 1,10-Phenanthroline d- or f-metal complexes can be utilised in biomedical applications such as imaging or therapeutics. Herein, we designed bimetallic d-block metal-phenanthroline f-block metal-1,4,7,10-tetraazacyclododecane-1,4,7,1,0-tetraacetic acid (DOTA) conjugates as theranostic agents to simultaneously achieve both of these applications. Luminescence studies show the 1,10-phenanthroline-Eu(III)-DOTA complexes displayed an off/on/off pH-dependent switch, demonstrating their potential as pH-responsive lanthanide luminescence probes. Relaxometry studies showed that the 1,10-phenanthroline-Gd(III)-DOTA complexes present a r1 of 5.15±0.05 mM−1 s−1 and could thus be used as magnetic resonance (MR) contrast agents. Complexation of Pt(II) by the 1,10-phenanthroline moiety resulted in quenching of the Eu(III) luminescence, but an enhancement of the Gd(III) relaxivity (r1=7.53±0.69 mM−1 s−1). Cell viability studies of the d–f hybrids in a cancer cell line showed the potential of these complexes as anticancer agents, as the IC50 for the Pt(II)/Gd(III) complex (IC50=24.9 μM) was lower than that of cisplatin (IC50=31.6 μM). As such, Pt(II)-1,10-phenanthroline-Gd(III)-DOTA complexes are promising theranostic agents for cancer therapy.

AB - 1,10-Phenanthroline d- or f-metal complexes can be utilised in biomedical applications such as imaging or therapeutics. Herein, we designed bimetallic d-block metal-phenanthroline f-block metal-1,4,7,10-tetraazacyclododecane-1,4,7,1,0-tetraacetic acid (DOTA) conjugates as theranostic agents to simultaneously achieve both of these applications. Luminescence studies show the 1,10-phenanthroline-Eu(III)-DOTA complexes displayed an off/on/off pH-dependent switch, demonstrating their potential as pH-responsive lanthanide luminescence probes. Relaxometry studies showed that the 1,10-phenanthroline-Gd(III)-DOTA complexes present a r1 of 5.15±0.05 mM−1 s−1 and could thus be used as magnetic resonance (MR) contrast agents. Complexation of Pt(II) by the 1,10-phenanthroline moiety resulted in quenching of the Eu(III) luminescence, but an enhancement of the Gd(III) relaxivity (r1=7.53±0.69 mM−1 s−1). Cell viability studies of the d–f hybrids in a cancer cell line showed the potential of these complexes as anticancer agents, as the IC50 for the Pt(II)/Gd(III) complex (IC50=24.9 μM) was lower than that of cisplatin (IC50=31.6 μM). As such, Pt(II)-1,10-phenanthroline-Gd(III)-DOTA complexes are promising theranostic agents for cancer therapy.

KW - cancer therapy

KW - Magnetic resonance imaging

KW - phenanthroline

KW - platinum

KW - theranostics

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U2 - 10.1002/ejic.202400063

DO - 10.1002/ejic.202400063

M3 - Article

AN - SCOPUS:85193632209

SN - 1434-1948

VL - 27

JO - EUROPEAN JOURNAL OF INORGANIC CHEMISTRY

JF - EUROPEAN JOURNAL OF INORGANIC CHEMISTRY

IS - 17

M1 - e202400063

ER -

Pt(II)-Phenanthroline-Ln(III)-DOTA d–f Hybrids as Small-Molecule Theranostics

Abstract

Keywords

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