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Spontaneous CO Release from Ru II (CO) 2 –Protein Complexes in Aqueous Solution, Cells, and Mice
Author(s) -
ChavesFerreira Miguel,
Albuquerque Inês S.,
MatakVinkovic Dijana,
Coelho Ana C.,
Carvalho Sandra M.,
Saraiva Lígia M.,
Romão Carlos C.,
Bernardes Gonçalo J. L.
Publication year - 2015
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201409344
Subject(s) - chemistry , in vivo , bovine serum albumin , aqueous solution , tumor necrosis factor alpha , downregulation and upregulation , biophysics , biochemistry , biology , endocrinology , microbiology and biotechnology , gene
We demonstrate that Ru II (CO) 2 –protein complexes, formed by the reaction of the hydrolytic decomposition products of [ fac ‐RuCl( κ 2 ‐H 2 NCH 2 CO 2 )(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)–Ru II (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–Ru II (CO) 2 in mice bearing a colon carcinoma tumor results in enhanced CO accumulation at the tumor. Our data suggest the use of Ru II (CO) 2 –protein complexes as viable alternatives for the safe and spatially controlled delivery of therapeutic CO in vivo.