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ChemMedChem. 2019 Jan 23. doi: 10.1002/cmdc.201800805. [Epub ahead of print]

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

Author information

1
Department of Chemical Sciences, University of Naples Federico II, Complesso Universitario di Monte Sant'Angelo, via Cinthia 21, 80126, Naples, Italy.
2
EMBL, CS 90181, 71 AV des Martyrs, 38009, Grenoble (38), France.
3
Department of Chemistry and Biochemistry, University of Bern, Freiestrasse 3, 3012, Bern, Switzerland.
4
Department of Organic Chemistry, Faculty of Chemistry, University of Łódź, Tamka 12, 91-403, Poland.

Abstract

The effects of encapsulating the cytotoxic dinuclear trithiolato-bridged arene ruthenium complex [(η6 -p-MeC6 H4 iPr)2 Ru22 -S-p-C6 H4 tBu)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.

KEYWORDS:

anticancer; diruthenium; drug delivery; ferritin; protein cages

PMID:
30674089
DOI:
10.1002/cmdc.201800805

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