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
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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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/ejic.202400063

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@article{a47c499c43f14fbd86acb048c541ddbe,

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.",

year = "2024",

month = jun,

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doi = "10.1002/ejic.202400063",

language = "English",

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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.

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

UR - http://www.scopus.com/inward/record.url?scp=85193632209&partnerID=8YFLogxK

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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