Spontaneous CO release from RuII(CO)2-protein complexes in aqueous solution, cells, and mice

Miguel Chaves-Ferreira, Inês S. Albuquerque, Dijana Matak-Vinkovic, Ana C. Coelho, Sandra M. Carvalho, Lígia M. Saraiva, Carlos Jose Romao, Gonc¸alo J L Bernardes

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

We demonstrate that RuII(CO)2-protein complexes, formed by the reaction of the hydrolytic decomposition products of [fac-RuCl(κ2-H2NCH2CO2)(CO)3] (CORM-3) with histidine residues exposed on the surface of proteins, spontaneously release CO in aqueous solution, cells, and mice. CO release was detected by mass spectrometry (MS) and confocal microscopy using a CO-responsive turn-on fluorescent probe. These findings support our hypothesis that plasma proteins act as CO carriers after in vivo administration of CORM-3. CO released from a synthetic bovine serum albumin (BSA)-RuII(CO)2 complex leads to downregulation of the cytokines interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-α in cancer cells. Finally, administration of BSA-RuII(CO)2 in mice bearing a colon carcinoma tumor results in enhanced CO accumulation at the tumor. Our data suggest the use of RuII(CO)2-protein complexes as viable alternatives for the safe and spatially controlled delivery of therapeutic CO in vivo.

Original languageEnglish
Pages (from-to)1172-1175
Number of pages4
JournalAngewandte Chemie-International Edition
Volume54
Issue number4
DOIs
Publication statusPublished - 19 Jan 2015

Keywords

  • Albumin
  • Carbon monoxide
  • CORM
  • Metalloproteins
  • Prodrugs

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