Cytotoxicity, cellular uptake, and subcellular localization of a nitrogen oxide and aminopropyl-beta-lactose derivative ruthenium complex used as nitric oxide delivery agent

Author(s)

dos Santos, Joicy Santamalvina ^{[1, 2]} ; Ramos, Loyanne C. ^[1] ; Ferreira, Lucimara P. ^[3] ; Campo, Vanessa Leira ^{[1, 4]} ; de Rezende, Lucas C. D. ^[1] ; Emery, Flavio da Silva ^[1] ; da Silva, Roberto Santana ^[1]

Affiliation

^[1] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Fis & Quim, Av Prof Zeferino Vaz S-N, BR-14040903 Ribeirao Preto, SP - Brazil

^[2] Univ Fed Bahia, Inst Quim, Dept Quim Geral & Inorgan, Rua Barao Geremoabo, 147 Campus Univ Ondina, BR-40170115 Salvador, BA - Brazil

^[3] Univ Sao Paulo, Fac Filosofia Ciencias & Letras Ribeirao Preto, Dept Fis, Av Bandeirantes 3900, BR-14040901 Ribeirao Preto, SP - Brazil

^[4] Barao Maua Univ Ctr, 423 Ramos de Azevedo St, BR-14090180 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: NITRIC OXIDE-BIOLOGY AND CHEMISTRY; v. 86, p. 38-47, MAY 1 2019.
• Web of Science Citations: 2

Abstract

This work investigates how the luminescent ruthenium-nitrite complexes cis-(Ru(PY-bodipy)(dcbpy)(2)(NO2)] (PF6) (I) and cis-(Ru(py-bodipy)(dcbpy-aminopropyl-beta-lactose)(2)(NO2)](PF6) (II) behave toward the melanoma cancer cell line B16F10. The chemical structure and purity of the synthesized complexes were analyzed by UV-Visible and FTIR spectroscopy, MALDI, HPLC, and H-1 NMR. Spectrofluorescence helped to determine the fluorescence quantum yields and lifetimes of each of these complexes. In vitro MTT cell viability assay on B16F10 cancer cells revealed that the complexes possibly have a tumoricidal role. The metal-nitrite complexes evidenced the dichotomous NO nature: at high concentration, NO exerted a tumoricidal effect, whereas cancer cells grew at low NO concentration. Flow cytometry or fluorescence microscopy aided cellular uptake calculation. Cell staining followed by fluorescence microscopy associated with organelle markers such as DAPI and Rhodamine 123 detected preferential intracellular localization of the ruthenium-nitrite py-bodipy and aminopropyl lactose derivative ruthenium complex in mitochondria. Thus, the cytotoxicity of compounds (I) and (II) against B16F10 cancer cell line show concentration-dependent results. The present studies suggest that nitric oxide ruthenium derivative compounds could be new potential chemotherapeutic agents against cytotoxic cells. (AU)

• FAPESP's process: 16/12707-0 - Cytotoxicity and photo-cytotoxicity of new ruthenium-phthalocyanines compounds as nitric oxide and oxygen singlet producers in cancer cell lines. an innovative purpose for metal based drug
• Grantee: Roberto Santana da Silva
• Support Opportunities: Regular Research Grants