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Encapsulation of the Dinuclear Trithiolato-Bridged Arene Ruthenium Complex Diruthenium-1 in an Apoferritin Nanocage : Structure and Cytotoxicity

Petruk, Ganna LU orcid ; Monti, Daria Maria ; Ferraro, Giarita ; Pica, Andrea ; D'Elia, Luigi ; Pane, Francesca ; Amoresano, Angela ; Furrer, Julien ; Kowalski, Konrad and Merlino, Antonello (2019) In ChemMedChem 14(5). p.594-602
Abstract

The effects of encapsulating the cytotoxic dinuclear trithiolato-bridged arene ruthenium complex [(η6-p-MeC6H4iPr)2Ru2(μ2-S-p-C6H4tBu)3]Cl (DiRu-1) within the apoferritin (AFt) nanocage were investigated. The DiRu-1-AFt nanocarrier was characterized by UV/Vis spectroscopy, ICP-MS, CD and X-ray crystallography. In contrast to previously reported Au- and Pt-based drug-loaded AFt carriers, we found no evidence of direct interactions between DiRu-1 and AFt. DiRu-1-AFt is cytotoxic toward immortalized murine BALB/c-3T3 fibroblasts transformed with SV40 virus (SVT2) and human epidermoid carcinoma A431 malignant cells, and exhibits moderate... (More)

The effects of encapsulating the cytotoxic dinuclear trithiolato-bridged arene ruthenium complex [(η6-p-MeC6H4iPr)2Ru2(μ2-S-p-C6H4tBu)3]Cl (DiRu-1) within the apoferritin (AFt) nanocage were investigated. The DiRu-1-AFt nanocarrier was characterized by UV/Vis spectroscopy, ICP-MS, CD and X-ray crystallography. In contrast to previously reported Au- and Pt-based drug-loaded AFt carriers, we found no evidence of direct interactions between DiRu-1 and AFt. DiRu-1-AFt is cytotoxic toward immortalized murine BALB/c-3T3 fibroblasts transformed with SV40 virus (SVT2) and human epidermoid carcinoma A431 malignant cells, and exhibits moderate selectivity for these cancer cells over normal BALB/c-3T3 cells. DiRu-1-AFt triggers the production of reactive oxygen species, depolarization of mitochondrial membrane potential, and induces cell death via p53-mediated apoptosis. Comparison between our data and previous results suggests that the presence of specific interactions between a metal-based drug and AFt within the protein cage is not essential for drug encapsulation.

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author
; ; ; ; ; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
keywords
anticancer, diruthenium, drug delivery, ferritin, protein cages
in
ChemMedChem
volume
14
issue
5
pages
594 - 602
publisher
Wiley-Blackwell
external identifiers
  • pmid:30674089
  • scopus:85061618564
ISSN
1860-7179
DOI
10.1002/cmdc.201800805
language
English
LU publication?
no
additional info
Publisher Copyright: © 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
id
648acafc-d4b6-4375-bf91-4d9fc086e105
date added to LUP
2025-01-21 15:39:57
date last changed
2025-05-23 11:02:14
@article{648acafc-d4b6-4375-bf91-4d9fc086e105,
  abstract     = {{<p>The effects of encapsulating the cytotoxic dinuclear trithiolato-bridged arene ruthenium complex [(η<sup>6</sup>-p-MeC<sub>6</sub>H<sub>4</sub>iPr)<sub>2</sub>Ru<sub>2</sub>(μ<sub>2</sub>-S-p-C<sub>6</sub>H<sub>4</sub>tBu)<sub>3</sub>]Cl (DiRu-1) within the apoferritin (AFt) nanocage were investigated. The DiRu-1-AFt nanocarrier was characterized by UV/Vis spectroscopy, ICP-MS, CD and X-ray crystallography. In contrast to previously reported Au- and Pt-based drug-loaded AFt carriers, we found no evidence of direct interactions between DiRu-1 and AFt. DiRu-1-AFt is cytotoxic toward immortalized murine BALB/c-3T3 fibroblasts transformed with SV40 virus (SVT2) and human epidermoid carcinoma A431 malignant cells, and exhibits moderate selectivity for these cancer cells over normal BALB/c-3T3 cells. DiRu-1-AFt triggers the production of reactive oxygen species, depolarization of mitochondrial membrane potential, and induces cell death via p53-mediated apoptosis. Comparison between our data and previous results suggests that the presence of specific interactions between a metal-based drug and AFt within the protein cage is not essential for drug encapsulation.</p>}},
  author       = {{Petruk, Ganna and Monti, Daria Maria and Ferraro, Giarita and Pica, Andrea and D'Elia, Luigi and Pane, Francesca and Amoresano, Angela and Furrer, Julien and Kowalski, Konrad and Merlino, Antonello}},
  issn         = {{1860-7179}},
  keywords     = {{anticancer; diruthenium; drug delivery; ferritin; protein cages}},
  language     = {{eng}},
  month        = {{03}},
  number       = {{5}},
  pages        = {{594--602}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{ChemMedChem}},
  title        = {{Encapsulation of the Dinuclear Trithiolato-Bridged Arene Ruthenium Complex Diruthenium-1 in an Apoferritin Nanocage : Structure and Cytotoxicity}},
  url          = {{http://dx.doi.org/10.1002/cmdc.201800805}},
  doi          = {{10.1002/cmdc.201800805}},
  volume       = {{14}},
  year         = {{2019}},
}