Redox double-switch cancer theranostics through Pt(iv) functionalised manganese dioxide nanostructures

Beatriz Brito; Maria Rosaria Ruggiero; Thomas W. Price; Milene da Costa Silva; Núria Genicio; Annah J. Wilson; Olga Tyurina; Veronika Rosecker; Thomas R. Eykyn; Manuel Bañobre-López; Graeme J. Stasiuk; Juan Gallo

doi:10.1039/d3nr00076a

Redox double-switch cancer theranostics through Pt(iv) functionalised manganese dioxide nanostructures

Beatriz Brito, Maria Rosaria Ruggiero, Thomas W. Price, Milene da Costa Silva, Núria Genicio, Annah J. Wilson, Olga Tyurina, Veronika Rosecker, Thomas R. Eykyn, Manuel Bañobre-López, Graeme J. Stasiuk, Juan Gallo^*

^*Corresponding author for this work

Imaging Chemistry & Biology

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

11 Citations (Scopus)

Abstract

Manganese dioxide (MnO₂)-based nanostructures have emerged as promising tumour microenvironment (TME) responsive platforms. Herein, we used a one-pot reaction to prepare MnO₂ nanostructures with Pt(iv) prodrugs as redox- (and thus TME-) responsive theranostics for cancer therapy, in which the Pt(iv) complexes act as prodrugs of cisplatin (Pt(ii)), a clinical chemotherapeutic drug. The cytotoxicity of these MnO₂-Pt(iv) probes was evaluated in two and three dimensional (2D and 3D) A549 cell models and found to be as effective as active drug cisplatin in 3D models. Moreover, MnO₂-Pt(iv) nanoparticles exhibited strong off/ON magnetic resonance (MR) contrast in response to reducing agents, with the longitudinal relaxivity (r₁) increasing 136-fold upon treatment with ascorbic acid. This off/ON MR switch was also observed in (2D and 3D) cells in vitro. In vivo MRI experiments revealed that the nanostructures induce a strong and long-lasting T₁ signal enhancement upon intratumoral injection in A549 tumour-bearing mice. These results show the potential of MnO₂-Pt(iv) NPs as redox responsive MR theranostics for cancer therapy.

Original language	English
Pages (from-to)	10763-10775
Number of pages	13
Journal	Nanoscale
Volume	15
Issue number	25
DOIs	https://doi.org/10.1039/d3nr00076a
Publication status	Published - 13 Jun 2023

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title = "Redox double-switch cancer theranostics through Pt(iv) functionalised manganese dioxide nanostructures",

abstract = "Manganese dioxide (MnO2)-based nanostructures have emerged as promising tumour microenvironment (TME) responsive platforms. Herein, we used a one-pot reaction to prepare MnO2 nanostructures with Pt(iv) prodrugs as redox- (and thus TME-) responsive theranostics for cancer therapy, in which the Pt(iv) complexes act as prodrugs of cisplatin (Pt(ii)), a clinical chemotherapeutic drug. The cytotoxicity of these MnO2-Pt(iv) probes was evaluated in two and three dimensional (2D and 3D) A549 cell models and found to be as effective as active drug cisplatin in 3D models. Moreover, MnO2-Pt(iv) nanoparticles exhibited strong off/ON magnetic resonance (MR) contrast in response to reducing agents, with the longitudinal relaxivity (r1) increasing 136-fold upon treatment with ascorbic acid. This off/ON MR switch was also observed in (2D and 3D) cells in vitro. In vivo MRI experiments revealed that the nanostructures induce a strong and long-lasting T1 signal enhancement upon intratumoral injection in A549 tumour-bearing mice. These results show the potential of MnO2-Pt(iv) NPs as redox responsive MR theranostics for cancer therapy.",

author = "Beatriz Brito and Ruggiero, {Maria Rosaria} and Price, {Thomas W.} and {da Costa Silva}, Milene and N{\'u}ria Genicio and Wilson, {Annah J.} and Olga Tyurina and Veronika Rosecker and Eykyn, {Thomas R.} and Manuel Ba{\~n}obre-L{\'o}pez and Stasiuk, {Graeme J.} and Juan Gallo",

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month = jun,

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doi = "10.1039/d3nr00076a",

language = "English",

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T1 - Redox double-switch cancer theranostics through Pt(iv) functionalised manganese dioxide nanostructures

AU - Brito, Beatriz

AU - Ruggiero, Maria Rosaria

AU - Price, Thomas W.

AU - da Costa Silva, Milene

AU - Genicio, Núria

AU - Wilson, Annah J.

AU - Tyurina, Olga

AU - Rosecker, Veronika

AU - Eykyn, Thomas R.

AU - Bañobre-López, Manuel

AU - Stasiuk, Graeme J.

AU - Gallo, Juan

PY - 2023/6/13

Y1 - 2023/6/13

N2 - Manganese dioxide (MnO2)-based nanostructures have emerged as promising tumour microenvironment (TME) responsive platforms. Herein, we used a one-pot reaction to prepare MnO2 nanostructures with Pt(iv) prodrugs as redox- (and thus TME-) responsive theranostics for cancer therapy, in which the Pt(iv) complexes act as prodrugs of cisplatin (Pt(ii)), a clinical chemotherapeutic drug. The cytotoxicity of these MnO2-Pt(iv) probes was evaluated in two and three dimensional (2D and 3D) A549 cell models and found to be as effective as active drug cisplatin in 3D models. Moreover, MnO2-Pt(iv) nanoparticles exhibited strong off/ON magnetic resonance (MR) contrast in response to reducing agents, with the longitudinal relaxivity (r1) increasing 136-fold upon treatment with ascorbic acid. This off/ON MR switch was also observed in (2D and 3D) cells in vitro. In vivo MRI experiments revealed that the nanostructures induce a strong and long-lasting T1 signal enhancement upon intratumoral injection in A549 tumour-bearing mice. These results show the potential of MnO2-Pt(iv) NPs as redox responsive MR theranostics for cancer therapy.

AB - Manganese dioxide (MnO2)-based nanostructures have emerged as promising tumour microenvironment (TME) responsive platforms. Herein, we used a one-pot reaction to prepare MnO2 nanostructures with Pt(iv) prodrugs as redox- (and thus TME-) responsive theranostics for cancer therapy, in which the Pt(iv) complexes act as prodrugs of cisplatin (Pt(ii)), a clinical chemotherapeutic drug. The cytotoxicity of these MnO2-Pt(iv) probes was evaluated in two and three dimensional (2D and 3D) A549 cell models and found to be as effective as active drug cisplatin in 3D models. Moreover, MnO2-Pt(iv) nanoparticles exhibited strong off/ON magnetic resonance (MR) contrast in response to reducing agents, with the longitudinal relaxivity (r1) increasing 136-fold upon treatment with ascorbic acid. This off/ON MR switch was also observed in (2D and 3D) cells in vitro. In vivo MRI experiments revealed that the nanostructures induce a strong and long-lasting T1 signal enhancement upon intratumoral injection in A549 tumour-bearing mice. These results show the potential of MnO2-Pt(iv) NPs as redox responsive MR theranostics for cancer therapy.

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JO - Nanoscale

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ER -

Redox double-switch cancer theranostics through Pt(iv) functionalised manganese dioxide nanostructures

Abstract

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