Self-Assembled Nanoparticles of Diruthenium(II,III)-Ibuprofen Anticancer Metallodrug

Author(s)

Marcio Hayashi ^[1] ; Samara R. Alves ^[2] ; Iguatinã M. Costa ^[3] ; Denise de Oliveira Silva ^[4]

Affiliation

^[1] Universidade de São Paulo. Instituto de Química. Departamento de Química Fundamental - Brasil

^[2] Universidade de São Paulo. Instituto de Química. Departamento de Química Fundamental - Brasil

^[3] Universidade de São Paulo. Instituto de Química. Departamento de Química Fundamental - Brasil

^[4] Universidade de São Paulo. Instituto de Química. Departamento de Química Fundamental - Brasil

• Document type: Journal article
• Source: Journal of the Brazilian Chemical Society; v. 31, n. 11, p. 2331-2341, 2020-10-30.

Abstract

The diruthenium(II,III)-ibuprofen (RuIbp) metallodrug shows anticancer activity in vitro and in vivo. The encapsulation into lipid nanoparticles enhanced the efficacy in glioblastoma, breast and prostate cancer cells. Here we report data for RuIbp hydrophobicity, solubility in alcohol/water, and behavior in 1-5% ethanol/water and ethanol/cell culture medium. RuIbp is capable of spontaneously generate self-assembled RuIbpNP nanoparticles when drug ethanolic solutions are added to water or cell growth culture medium at 1-5% ethanol. The phenomenon was investigated, and the nanoparticles characterized. RuIbpNP nanoparticles formed at 100-200 µmol L−1 RuIbp are colloidally stable and nearly spherical showing zeta potential about +40 mV and particle size about 100 (aqueous suspension) and 180 nm (culture medium). The integrity of the [Ru2(Ibp)4] framework was confirmed by spectroscopy and mass spectrometry. Significant amount of metallodrug was found in suspension (85%, culture medium; 54%, culture medium with cells). The uptake by U87MG glioblastoma cells was 6% at 24 h. The spontaneous nanosizing of RuIbp in the form of nanosuspensions may explain the biological activity of this highly hydrophobic metallodrug. The present findings expand the knowledge on the behavior of RuIbp, opening new directions to exploit the properties of the metallodrug targeting cancer therapy. (AU)

• FAPESP's process: 14/23481-7 - Study of lipid-based nanoparticles as carriers for anticancer ruthenium metallodrugs
• Grantee: Samara Rodrigues Alves
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 14/23047-5 - Anticancer metallodrugs of ruthenium containing bioactive ligands: synthesis, interaction with biomolecules and preparation of biocompatible nanoparticle drug delivery systems
• Grantee: Denise de Oliveira Silva
• Support Opportunities: Regular Research Grants
• FAPESP's process: 16/23028-6 - Study of the chemical behaviour of metallodrugs of diruthenium(II,III) containing anti-inflammatories
• Grantee: Marcio Hayashi
• Support Opportunities: Scholarships in Brazil - Scientific Initiation