Mauricio S Baptista

University of São Paulo, San Paulo, São Paulo, Brazil

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Publications (108)266.04 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The new tris-heteroleptic complex [Ru(bpy)(dppn)(CH3CN)2]2+ (3, bpy = 2,2´-bipyridine, dppn = benzo[i]dipyrido[3,2-a;2´,3´-c]-phenazine) was synthesized and characterized in an effort to generate a molecule capable of both singlet oxygen (1O2) production and ligand exchange upon irradiation. Such dual reactivity has the potential to be useful for increasing the efficacy of photochemotherapy (PCT) drugs by acting via two different mechanisms simultaneously. The photochemical properties and photoinduced cytotoxicity of 3 were compared to those of the [Ru(bpy)2(dppn)]2+ (1) and [Ru(bpy)2(CH3CN)2]2+ (2), since 1 sensitizes the production of 1O2 and 2 undergoes ligand exchange of the monodentate CH3CN ligands with solvent when irradiated. The quantum yield of 1O2 production was measured to be 0.72(2) for 3 in methanol, which is slightly lower than that of 1, 0.88(2), in the same solvent (λirr = 460 nm). Complex 3 also undergoes photoinduced ligand exchange when irradiated in H2O (λirr = 400 nm), but with a low quantum efficiency (< 1%). These results are explained by the low-lying ligand-centered 3ππ* excited state of 3 localized on the dppn ligand, thus decreasing the relative population of the higher energy 3dd state; the latter is associated with ligand dissociation. Cytotoxicity data with HeLa cells reveals that complex 3 exhibits a greater photocytoxicity index, 1,110, than do either 1 and 2, indicating that the dual action complex is more photoactive towards cells in spite of its low ligand exchange quantum yield.
    Journal of the American Chemical Society 11/2014; · 10.68 Impact Factor
  • Patricia A. Santos, Cleidiane S. Rocha, Mauricio S. Baptista
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    ABSTRACT: The development of materials that allow proper functioning of cells on solid supports is directly relevant to the construction of living-cell biosensors. Both physical and chemical properties of the surfaces have been shown to be critical in this field. Our aim is to report correlations between chemical properties of surfaces and cell behavior by studying adhesion, viability and proliferation of fibroblasts and HeLa cells. Neither fibroblasts nor HeLa cells adhered to a hydrophobic surface. Fibroblasts were able to attach and proliferate well on all other surfaces tested. In contrast, on some surfaces where HeLa cells adhered and were viable, proliferation decreased by half while on others proliferation was not affected. Proliferation was significantly correlated with the level of adsorption of serum proteins on the surface (quantified by surface plasmon resonance), but not with surface wettability (water contact angle). Interestingly, surfaces modified with COOH and HSO3 groups were the ones that favored most protein adsorption and allowed the best measures for HeLa cell proliferation. The decrease of HeLa cell proliferation on surfaces covered with poly-l-lysine (PL) was related with the profile of integrin expression. Compared to a polystyrene control surface, there was an increase in αV and αVβ3 and a decrease in α2 and α3, indicating that migration rather than proliferation could be favored on PL functionalized surfaces. These results indicate that charge is more important than wettability to determine biocompatibility. Copyright © 2014. Published by Elsevier B.V.
    Colloids and surfaces B: Biointerfaces 10/2014; · 4.28 Impact Factor
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    ABSTRACT: Silylation of riboflavin allowed its incorporation into spherical SiO2 nanoparticles that were able to generate singlet oxygen and oxidize human serum albumin while conferring riboflavin remarkable photostability.
    J. Mater. Chem. B. 06/2014; 2(27).
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    ABSTRACT: The chemistry of meso-tetrathienyl-substituted porphyrin derivatives was explored, including synthesis and subsequent metalation, nitration and 1,3-dipolar cycloaddition reactions. Mono- and tetra-nitro-meso-tetrathienylporphyrins were prepared selectively under mild nitration conditions with NaNO2 and trifluoroacetic acid, and the corresponding chlorins and bacteriochlorins were also obtained by reaction with 1,3-dipoles. The products were characterized in detail and their preliminary photophysical properties were evaluated.
    Annalen der Chemie und Pharmacie 06/2014; · 3.10 Impact Factor
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    ABSTRACT: Oxidation can intimately influence and structurally compromise the levels of biological self-assembly embodied by intracellular and plasma membranes. Lipid peroxidation, a natural metabolic outcome of life with oxygen under light, is also a salient oxidation reaction in photomedicine treatments. However, the effect of peroxidation on the fate of lipid membranes remains elusive. Here we use a new photosensitizer that anchors and disperses in the membrane to achieve spatial control of the oxidizing species. We find, surprisingly, that the integrity of unsaturated unilamellar vesicles is preserved even for fully oxidized membranes. Membrane survival allows for the quantification of the transformations of the peroxidized bilayers, providing key physical and chemical information to understand the effect of lipid oxidation on protein insertion and on other mechanisms of cell function. We anticipate that spatially controlled oxidation will emerge as a new powerful strategy for tuning and evaluating lipid membranes in biomimetic media under oxidative stress.
    Soft Matter 05/2014; 10(24):4241-7. · 4.15 Impact Factor
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    ABSTRACT: •We developed a low cost PDT protocol to treat the diabetic feet•Rate of amputation was 35 times smaller in the PDT group•Increased efficiency to treat diabetic feet can be of use in public health
    Photodiagnosis and photodynamic therapy 05/2014;
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    ABSTRACT: Leishmaniasis is a chronic disease affecting the skin, mucosal and/or internal organs, caused by flagellate protozoa Leishmania of the Trypanosomatidae family. [1] It is among the six most important disease in terms of its impact in public health. The world incidence of leishmaniasis is very large with about half a million new cases per year. About 12 million people are infected with Leishmania ssp parasites worldwide. New treatment alternatives are highly needed. Our goal here is to critically revise the literature in order to show the potential of Photodynamic Therapy in the treatment and comprehensive control of this disease. We have separated this chapter in nine sections, besides this brief introduction, which are: Leishmaniasis: Background and treatment strategies; Mechanisms in Photodynamic Therapy; Treatment of animals infected with leishmaniasis using PDT; Vector control using PDT; PDT alternatives for Blood purification; PDT on the treatment of Old World Tegumentary Leishmaniasis; PDT - In vitro tests in species that cause Tegumentary Leishmaniasis; Conclusions; References.
    Leishmaniasis - Trends in Epidemiology, Diagnosis and Treatment, Edited by David M. Claborn, 03/2014: chapter Treatment and Control of Leishmaniasis Using Photodynamic Therapy: pages 393-412; InTech., ISBN: 978-953-51-1232-7
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    ABSTRACT: Lipid coating is a method highly used to improve the biocompatibility of nanoparticles (NPs), even though its effect on the NP properties is still object of investigation. Herein, silica NPs containing methylene blue, which is a photosensitizer used in a variety of biomedical applications, were coated with a phospholipid bilayer. Regarding the photophysical properties, lipid-coating did not cause significant changes since bare and lipid-coated NPs presented very similar absorption spectra and generated singlet oxygen with similar efficiencies. However, NP interaction with cells and membrane mimics was totally different for bare and lipid-coated NPs. Lipid-coated NPs were distributed through the cell cytoplasm whereas bare NPs were detected only in some vacuolar regions within the cells. Since cellular uptake and cytolocalization are influenced by NP adsorption on cell membranes, the interaction of lipid-coated and bare NPs were studied on a membrane mimic, i.e., Hybrid Bilayer Membranes (HBMs) made of different compositions of negatively charged and neutral lipids. Interactions of bare and lipid-coated NPs with HBMs were analyzed by Surface Plasmon Resonance Imaging. Bare NPs presented high adsorption and aggregation on HBMs independently of the surface charge. Conversely, lipid-coated NPs presented less aggregation on the membrane surface and the adsorption was dependent on the charges of the NPs and of the HBMs. Our results indicated that NPs aggregation on the membrane surface can be modulated by lipid coating, which affects the cytosolic distribution of the NPs.
    Journal of Biomedical Nanotechnology 03/2014; 10(3):519-28. · 7.58 Impact Factor
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    ABSTRACT: Structure-activity relationships have been widely reported for porphyrin and phthalocyanine photosensitizers, but not for phenothiazinium derivatives. Here four phenothiazinium salts (methylene blue, toluidine blue O, 1,9-dimethyl methylene blue and the pentacyclic derivative DO15) were used to investigate how the ability to damage membranes is affected by membrane/solution partition, photophysical properties and tendency to aggregation of the photosensitizer. These two latter aspects were studied both in isotropic solutions and in membranes. Membrane damage was assessed by leakage of a fluorescent probe entrapped in liposomes and by generation of thiobarbituric acid-reactive species (TBARS), while structural changes at the lipid bilayer were detected by small angle X-ray scattering. We observed that all compounds had similar singlet oxygen quantum yields in ethanol, but only the photosensitizers that had higher membrane/solution partition (1,9-dimethyl methylene blue and DO15, the latter having the higher value) could permeabilize the lipid bilayer. Moreover, of these two photosensitizers, only DO15 altered membrane structure, a result that was attributed to its destabilization of higher order aggregates, generation of higher amounts of singlet oxygen within the membranes and effective electron transfer reaction within its dimers. We concluded that membrane-based protocols can provide a better insight on the PDT efficiency of the photosensitizer. This article is protected by copyright. All rights reserved.
    Photochemistry and Photobiology 02/2014; · 2.29 Impact Factor
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    ABSTRACT: The antiproliferative activity of four Ru(II) dyes incorporating the cyclometallated ligand phpy– (deprotonated 2-phenylpyridine) have been tested against HeLa cells. All of the compounds exhibit cytotoxic activity similar to that of cisplatin. The most active compound, [Ru(phpy)(bpy)(dppn)]+ (4; bpy = 2,2′-bipyridine, dppn = benzo[i]dipyrido[3,2-a:2′,3′-c]phenazine), is 6 times more active than the platinum drug, and it is able to disrupt the mitochondria membrane potential. In addition, [Ru(phpy)(biq)2]+ (3; biq = 2,2′-biqinoline), with strong absorption at 640 nm, exhibits enhanced activity upon irradiation with 633 nm light. These findings demonstrate that coordinatively saturated cyclometallated Ru dyes have the potential to emerge as a new family of organometallic anticancer compounds, both in the dark and upon irradiation with low-energy light. The compound [Ru(phpy)(pap)(NCCH3)2]+ (5; pap = 2-(phenylazo)pyridine) was also synthesized and structurally characterized as a new precursor for the preparation of tris-heteroleptic dyes.
    Organometallics 02/2014; 33(5):1100–1103. · 4.15 Impact Factor
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    ABSTRACT: Antimicrobial photodynamic therapy (APDT) may become a useful clinical tool to treat microbial infections, and methylene blue (MB) is a well-known photosensitizer constantly employed in APDT studies, and although MB presents good efficiency in antimicrobial studies, some of the MB photochemical characteristics still have to be evaluated in terms of APDT. This work aimed to evaluate the role of MB solvent's ionic strength regarding dimerization, photochemistry, and photodynamic antimicrobial efficiency. Microbiological survival fraction assays on Escherichia coli were employed to verify the solution's influence on MB antimicrobial activity. MB was evaluated in deionized water and 0.9% saline solution through optical absorption spectroscopy; the solutions were also analysed via dissolved oxygen availability and reactive oxygen species (ROS) production. Our results show that bacterial reduction was increased in deionized water. Also we demonstrated that saline solution presents less oxygen availability than water, the dimer/monomer ratio for MB in saline is smaller than in water and MB presented a higher production of ROS in water than in 0.9% saline. Together, our results indicate the importance of the ionic strength in the photodynamic effectiveness and point out that this variable must be taken into account to design antimicrobial studies and to evaluate similar studies that might present conflicting results.
    Photochemical and Photobiological Sciences 02/2014; · 2.92 Impact Factor
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    ABSTRACT: Pythiosis is an infectious disease caused by Pythium insidiosum, a fungus-like organism. Due to the lack of ergosterol on its cell membrane, antibiotic therapy is ineffective. The conventional treatment is surgery, but lesion recurrence is frequent, requiring several resections or limb amputation. Photodynamic therapy uses photo-activation of drugs and has the potential to be an attractive alternative option. The in vitro PDT response on the growing of Pythium insidiosum culture was investigated using three distinct photosensitizers: methylene blue, Photogem, and Photodithazine. The photosensitizer distribution in cell structures and the PDT response for incubation times of 30, 60, and 120 minutes were evaluated. Methylene blue did not penetrate in the pathogen's cell and consequently there was no PDT inactivation. Photogem showed heterogenous distribution in the hyphal structure with small concentration inside the cells. Porphyrin-PDT response was heterogenous, death and live cells were observed in the treated culture. After 48 hours, hyphae regrowth was observed. Photodithazine showed more homogenous distribution inside the cell and with the specific intracellular localization dependent on incubation time. Photodithazine first accumulates in intracellular vacuoles, and at incubation times of one hour, it is located at all cell membranes. Higher inhibition of the growing rates was achieved with Photodithazine -PDT, over 98%. Our results showed that the photosensitizers that cross more efficiently the Pythium insidiosum membranes are able to cause extensive damage to the organism under illumination and therefore, are the best options for clinical treatment.
    PLoS ONE 01/2014; 9(1):e85431. · 3.53 Impact Factor
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    ABSTRACT: In this study we pursue a closer analysis of the photodamage promoted on giant unilamellar vesicles membranes made of dioleoyl-sn-glycero-3-phosphocholine (DOPC) or 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), by irradiating methylene blue present in the giant unilamellar vesicles solution. By means of optical microscopy and electro-deformation experiments, the physical damage on the vesicle membrane was followed and the phospholipids oxidation was evaluated in terms of changes in the membrane surface area and permeability. As expected, oxidation modifies structural characteristics of the phospholipids that lead to remarkable membrane alterations. By comparing DOPC- with POPC-made membranes, we observed that the rate of pore formation and vesicle degradation as a function of methylene blue concentration follows a diffusion law in the case of DOPC and a linear variation in the case of POPC. We attributed this scenario to the nucleation process of oxidized species following a diffusion-limited growth regime for DOPC and in the case of POPC a homogeneous nucleation process. On the basis of these premises, we constructed models based on reaction-diffusion equations that fit well with the experimental data. This information shows that the outcome of the photosensitization reactions is critically dependent on the type of lipid present in the membrane.
    Biophysical Journal 01/2014; 106(1):162-71. · 3.67 Impact Factor
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    ABSTRACT: Protecting human skin from sun exposure is a complex issue that involves unclear aspects of the interaction between light and tissue. A persistent misconception is that visible light is safe for the skin, although several lines of evidence suggest otherwise. Here, we show that visible light can damage melanocytes through melanin photosensitization and singlet oxygen (1O2) generation, thus decreasing cell viability, increasing membrane permeability, and causing both DNA photo-oxidation and necro-apoptotic cell death. UVA (355 nm) and visible (532 nm) light photosensitize 1O2 with similar yields, and pheomelanin is more efficient than eumelanin at generating 1O2 and resisting photobleaching. Although melanin can protect against the cellular damage induced by UVB, exposure to visible light leads to pre-mutagenic DNA lesions (i.e., Fpg- and Endo III-sensitive modifications); these DNA lesions may be mutagenic and may cause photoaging, as well as other health problems, such as skin cancer.
    PLoS ONE 01/2014; 9(11):e113266. · 3.53 Impact Factor
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    ABSTRACT: Estimation of the time period that precedes an injury is critical in forensic medicine. However, there is no reliable method that can be used to evaluate the oldness of a lesion. The aim of this work is to develop a fluorimetric method that can be used to follow the aging process of lesions by applying methyl-ALA (MAL) on wounds and by quantifying protoporphyrin IX (PPIX) fluorescence during the healing process. We also aim to understand the changes in PPIX fluorescence by establishing a correlation with histological evaluations during the healing process. Standardized linear wounds were made on the dorsum of 72 mice, which were divided in control (MAL -) and experimental (MAL +) groups. In vivo fluorescence spectra (FS) were collected from normal and wound skin sites of control and experimental groups, corresponding to four groups of FS spectra: (a) FS of skin wound after MAL (+/+); (b) FS of normal skin after MAL (-/+); (c) FS of skin wound without MAL (+/-) and (d) FS of normal skin without MAL (-/-). Animals were monitored periodically for 3 months and euthanized. Tissue specimens were processed for histological analysis using design-based stereological methods. Serial cross-sections were analyzed to evaluate the organization of the dermis and epidermis, collagen deposition and cellular proliferation. FS of skin wound with MAL (+/+) showed an expressive intensity increase from the beginning of the experiment to the 34th day, with maximum fluorescence being observed on the ∼11th day after wounding. There was preferential PPIX accumulation in healing sites as compared to adjacent normal skin (+/-) in the early stage of healing. Histological findings allowed correlation of the fluorescence increase mainly with cell proliferation. The drastic decrease in the FS intensity observed in the end of the healing process was correlated with the decrease in the proliferation rate as well as with the presence of new extracellular fibrous materials. In the mice wound-healing model tested here, it was possible to distinguish whether the injury was in early or advanced stages by using PPIX fluorescence induced by MAL. We conclude that this method is a promising approach to evaluate the age of skin wounding and we hope this work will stimulate human studies to allow this technique to become standardized in forensic medicine.
    Photodiagnosis and photodynamic therapy 12/2013; 10(4):389-398.
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    ABSTRACT: The most challenging and wanted development in photodynamic therapy is the control of photosensitizer (PS) cytolocalization and the mechanism of cell death. 5,10,15-triphenyl-20-(3-N-methylpyridinium-yl)porphyrin (3MMe) administered to HeLa cells as DMSO solution accumulates in the cytoplasmic membrane (CM) where it causes severe photodamage and cell necrosis. In contrast, when incorporated in marine atelocollagen/xantham gum polymeric nanocapsules, the PS is shuttled through CM allowing its gradual release and accumulation in mitochondria and lysosomes. Little photodamage was caused to cells in this case, but compelling evidences are presented showing that encapsulation changes the cytolocalization and shifts the cell death mechanism from necrosis to apoptosis. In conclusion, both of those challenges can be overcome by encapsulation of typical PSs such as 3MMe by using the new concept of photodynamic treatment with minimal cell damage by targeting specifically some key organelles. We are confident that these findings are important for the development of more efficient photosensitizers tailored to induce apoptosis while minimizing undesirable side effects such as over-inflammation.
    Journal of Biomedical Nanotechnology 08/2013; 9(8):1307-17. · 7.58 Impact Factor
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    ABSTRACT: Recent progress in understanding the molecular basis of autophagy has demonstrated its importance in several areas of human health. However, affordable screening techniques with higher sensitivity and specificity to identify autophagy are needed to move the field forward. In fact, only laborious and/or expensive methodologies such as electron microscopy, dye-staining of autophagic vesicles and LC3-II immunoblotting or immunoassaying are available for autophagy identification. Aiming to fulfill this technical gap, we described here the association of three widely used assays to determine cell viability - CVS (crystal violet staining), MTT reduction (3-[4, 5-dimethylthiaolyl]-2, 5-diphenyl-tetrazolium bromide) and NRU (neutral red uptake) - to predict autophagic cell death in vitro. The conceptual framework of the method is the superior uptake of NR in cells engaging in autophagy. NRU was then weighted by the average of MTT reduction and CVS allowing the calculation of AAU (autophagic arbitrary units), a numeric variable that correlated specifically with the autophagic cell death. The proposed strategy is very useful for drug discovery, allowing the investigation of potential autophagic inductor agents through a rapid screening using mammalian cell lines B16-F10, HaCaT, HeLa, MES-SA and MES-SA/Dx5 in a unique single microplate.
    Biotechnology Journal 02/2013; · 3.71 Impact Factor
  • P. P. Favero, A. C. Ferraz, Maurício S. Baptista, R. Miotto
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    ABSTRACT: In this work we propose the use of experimental and theoretical reflectance anisotropy spectra (RAS) as a new tool to identify structural and dynamical aspects of the bilipid membrane and its various constituent molecules. The role of geometric details at the atomic level and macroscopic quantities, such as the membrane curvature and tilt for the different gel phases, in the theoretical RAS spectra (using Kohn-Sham density functional theory (KS-DFT)) are presented. Then the results are compared to the experimentally measured spectra taken from other techniques.
    Proc SPIE 02/2013;
  • Rodrigo M Cordeiro, Ronei Miotto, Maurício S Baptista
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    ABSTRACT: Porphyrin derivatives have applications as photoactive drugs in photodynamic therapy. However, little is known about their interactions with phospholipid membranes at the molecular level. We employed molecular dynamics simulations to model the binding between a series of cationic meso-(N-methyl-4-pyridinium)phenylporphyrins and anionic phosphatidylglycerol lipid bilayers. This was done in the presence of molecular oxygen within the membrane. The ability of various porphyrins to cause photodamage was quantified in terms of their immersion depth and degree of exposition to a higher oxygen concentration inside the membrane. Simulations showed that the photodynamic efficiency could be improved as the number of hydrophobic phenyl substituents attached to the porphyrinic ring increased. In the specific case of porphyrins containing two hydrophobic and two charged substituents, the cis isomer was significantly more efficient than the trans. These results correlate well with previous experimental observations. They highlight the importance of both the total charge and amphiphilicity of the photosensitizer for its performance in photodynamic therapy.
    The Journal of Physical Chemistry B 11/2012; · 3.61 Impact Factor

Publication Stats

704 Citations
266.04 Total Impact Points

Institutions

  • 1999–2014
    • University of São Paulo
      • • Department of Biochemistry (IQ)
      • • Instituto de Química (IQ) (São Paulo)
      • • Instituto de Física (IF) (São Paulo)
      San Paulo, São Paulo, Brazil
  • 2012
    • Universidade Federal do ABC (UFABC)
      Santo André, São Paulo, Brazil
  • 2011
    • Liverpool John Moores University
      • School of Pharmacy and Biomolecular Sciences
      Liverpool, ENG, United Kingdom
  • 2009
    • Universidade Federal de São Paulo
      • Departamento de Biofísica
      São Paulo, Estado de Sao Paulo, Brazil
  • 2004–2007
    • Universidade de Mogi das Cruzes
      • Centro Interdisciplinar de investigação Bioquímica (CIIB)
      Moji das Cruzes, São Paulo, Brazil