[Todos] Seminarios DQIAQF - INQUIMAE, Viernes 08 de junio - 13 hs.

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Seminarios DQIAQF - INQUIMAE, Viernes 08 de junio - 13 hs.

Aula de Seminarios INQUIMAE - DQIAQF
Facultad de Ciencias Exactas y Naturales
Ciudad Universitaria - Pab. 2  -  Piso 3


 Synergistic effect of nitric oxide and singlet oxygen originated from
light irradiation on nitrosyl ruthenium complex as potentiation for
photodynamic therapy. Kinetic, photobiological and cytotoxicity studies

Professor Roberto Santana da Silva
*Pharmacy School*
*University of São Paulo - Brasil*


Nitric oxide (NO) is an important biological messenger. It has been
implicated in many physiological processes, including cardiovascular
control, neuronal signaling, defense against microorganism and tumors. It
can trigger pro- and antitumor responses depending on the concentration of
this molecule (NO) in biological system. The antitumor effect is pronounced
when there are high levels of NO in tumor cells, which make a challenge
develop compounds that can deliver NO under external stimulation. This work
describes synthesis, kinetic, photochemical and photobiological studies of
some nitrosyl ruthenium complex type [RuL5NO]n+ and  [RuL5NO]—antibody used
as NO deliver system. Conjugation antibody to {Ru-NO} improve site
specification on cell. The compound was obtained by covalent bond using
appropriate reagents and separation from free [RuL5NO] was achieved by
exclusion chromatography. Identification of Ru-NO—antibody was carried out
using Eastern Blotting test. Cell viability decreased to 12 % for
Ru-NO--IgG compound while aqueous [RuL5NO]2+ was found 85 %. It may be
related to the NO release in an appropriate target to kill cancer cell.
Apoptosis was described as the main biological mechanism for the nitrosyl
ruthenium complex. It is also being performed in our laboratories a
chemical investigation on trinuclear ruthenium carboxilates as nitric oxide
releasers. Up to now the compound [Ru3O(CH3COO)6(L)2NO]PF6 where L =
3-picoline releases NO upon irradiation at 377 nm, 447 nm and 532 nm, while
compound where L = 4-acetylpyridine, a pi-acceptor ligand, is unstable,
releasing NO even in the dark. Cell viability was also studied under light
irradiation effect of [RuL5NO] complex. One of this complex is [{(Ru(bpy2
)NO)}2(pz)Ru(Pc)pz)] (I) (where pc = phthalocyanine, bpy = 2,2’-bipyridine
and pz = pyrazine ligand) as putative system to improve photodynamic
therapy (PDT). This trinuclear compound display n(NO) at 1942 cm-1,
indicating that the nitrosyl group exhibits a sufficiently high degree of
nitrosonium ion (NO+) and show NO release under 650 nm light irradiation.Once
phthalocyanine compounds are widely used in PDT due to their capacity of
singlet oxygen generation, cytotoxicity assays against murine melanoma cell
line B16F10 were evaluated as well. The compound was able to inhibit
cellular viability when irradiated at 660 nm, compared with the treatment
without photo stimulus. Similar studies was also conduced with Quantum dot
coupled to nitrosyl ruthenium (QD-Ru) system. The generated QD-Ru was able
to produce NO by photoinduced eletron transfer as well singlet oxygen by
energy transfer. The cell viability were found between 10-25 % with 5 J/cm
of potency in ligh irradiation. The cell death is mainly attributed to the
apoptosis mechanism. The initial studies suggested us the NO production
increases the sensitivity of the cells to singlet oxygen. The synergistic
effect of NO and 1O2 may improve Photodynamic Therapy.