Gabriela Di Venosa

Hospital de Clínicas "José de San Martín"

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Trends

Author Order

Document Type

Co-Authors

Adriana Casas

Consejo Nacional de Investigaciones Científicas y Técnicas

Alcira Batlle

Consejo Nacional de Investigaciones Científicas y Técnicas

Leandro Mamone

Consejo Nacional de Investigaciones Científicas y Técnicas

Daniel A. Sáenz

University of Buenos Aires

Lorena Rodríguez

Parque Tecnológico de la Salud

Haydée Fukuda

University of Buenos Aires

Alexander J. MacRobert

University College London

Gustavo Calvo

Consejo Nacional de Investigaciones Científicas y Técnicas

Alcira Batlle

University of Buenos Aires

Pablo Vallecorsa

Comisión Nacional de Energía Atómica

Cooperative Institutions

Consejo Nacional de Investigaciones Científicas y Técnicas

University of Buenos Aires

Fundación Ciencias Exactas y Naturales

Hospital de Clínicas "José de San Martín"

Centro Científico Tecnológico - San Juan

Centro Científico Tecnológico - Tucumán

National University of Río Cuarto

Weatherford College

Institute of Astronomy and Space Physics

Universidad Nacional de Córdoba

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Field

Sensitivity to ALA-PDT of cell lines with different nitric oxide production and resistance to NO cytotoxicity

Journal of Photochemistry and Photobiology B Biology (2005)

Gabriela Di Venosa Christian Perotti Haydée Fukuda Alcira Batlle Adriana Casas

Sodium nitroprusside

10.1016/j.jphotobiol.2005.05.001

Cite

Citations (19)

The Use of Dipeptide Derivatives of 5-Aminolaevulinic Acid Promotes Their Entry to Tumor Cells and Improves Tumor Selectivity of Photodynamic Therapy

Molecular Cancer Therapeutics (2014)

Gabriela Di Venosa Pablo Vallecorsa Francesca Giuntini Leandro Mamone Alcira Batlle

The use of endogenous protoporphyrin IX generated after administration of 5-aminolaevulinic acid (ALA) has led to many applications in photodynamic therapy (PDT). However, the bioavailability of ALA is limited by its hydrophilic properties and limited cell uptake. A promising approach to optimize the efficacy of ALA-PDT is to deliver ALA in the form of prodrugs to mask its hydrophilic nature. The aim of this work was to evaluate the potential of two ALA dipeptide derivatives, N-acetyl terminated leucinyl-ALA methyl ester (Ac-Leu-ALA-Me) and phenylalanyl-ALA methyl ester (Ac-Phe-ALA-Me), for their use in PDT of cancer, by investigating the generation of protoporphyrin IX in an oncogenic cell line (PAM212-Ras), and in a subcutaneous tumor model. In our in vitro studies, both derivatives were more effective than ALA in PDT treatment, at inducing the same protoporphyrin IX levels but at 50- to 100-fold lower concentrations, with the phenylalanyl derivative being the most effective. The efficient release of ALA from Ac-Phe-ALA-Me appears to be consistent with the reported substrate and inhibitor preferences of acylpeptide hydrolase. In vivo studies revealed that topical application of the peptide prodrug Ac-Phe-ALA-Me gave greater selectivity than with ALA itself, and induced tumor photodamage, whereas systemic administration improved ALA-induced porphyrin generation in terms of equivalent doses administered, without induction of toxic effects. Our data support the possibility of using particularly Ac-Phe-ALA-Me both for topical treatment of basal cell carcinomas and for systemic administration. Further chemical fine-tuning of this prodrug template should yield additional compounds for enhanced ALA-PDT with potential for translation to the clinic.

Protoporphyrin IX

10.1158/1535-7163.mct-13-1084

Cite

Citations (14)

Mechanisms of 5‐aminolevulic acid ester uptake in mammalian cells

British Journal of Pharmacology (2006)

Lorena Rodríguez Alcira Batlle Gabriela Di Venosa Sinan Battah Paul S. Dobbin

The porphyrin precursor 5-aminolevulinic acid (ALA) is being widely used in photodynamic therapy of cancer. Improvement in ALA delivery has been sought through the use of ALA derivatives, in particular the esterification of ALA with aliphatic alcohols, which in certain cases can improve cellular penetration and selectivity. ALA uptake systems appear to be distinctive for each cell type. The LM3 mammary adenocarcinoma cell line takes ALA up by BETA transporters. In this work, we investigated ALA derivative transport systems through the inhibition of radiolabelled ALA uptake in the LM3 cells. We also performed inhibition studies of gamma-aminobutyric acid (GABA) uptake. The more lipohilic ALA derivatives hexyl-ALA and undecanoyl-ALA inhibit ALA uptake, whereas methyl-ALA, R, S-ALA-2-(hydroxymethyl)tetrahydropyranyl ester and the dendron aminomethane tris methyl 5-ALA does not inhibit ALA uptake. A similar pattern was found for GABA, except that the dendron inhibited GABA uptake. However, hexyl-ALA and undecanoyl-ALA are not taken up by BETA transporters, but by simple diffusion, although they still inhibit ALA uptake by binding to the cell membrane. These results show that different modifications to the ALA molecule lead to different uptake mechanisms. Whereas ALA is taken up by BETA transporters, none of the ALA derivatives shares the same mechanism. Knowledge of the mechanisms of ALA derivatives entry into the cells is essential to understand and improve ALA-mediated PDT and to the design of new ALA derivatives that may be taken up at a higher rate than ALA.

10.1038/sj.bjp.0706668

Cite

Citations (65)

Characterisation of liposomes containing aminolevulinic acid and derived esters

Journal of Photochemistry and Photobiology B Biology (2008)

Gabriela Di Venosa Laura Hermida Alcira Batlle Haydée Fukuda María Victoria Defain

Sonication

Phosphatidyl choline

Dilution

10.1016/j.jphotobiol.2008.03.008

Cite

Citations (49)

Laser NIR irradiation enhances antimicrobial photodynamic inactivation of biofilms of Staphylococcus aureus

Leandro Mamone Roberto Tomás Gabriela Di Venosa Lautaro Gándara Edgardo N. Durantini

ABSTRACT Photodynamic inactivation (PDI) utilizes a photosensitizer (PS) activated by visible light to generate reactive oxygen species (ROS), to kill bacteria. PDI is effective against planktonic microorganisms, but biofilms are less sensitive due to limited PS and oxygen penetration. Near-infrared treatment (NIRT), involve the use of near-infrared light to kill bacteria either via thermal effects or ROS production. Our objective was to enhance S. aureus biofilm’s sensitivity to PDI by pre-treating with NIR irradiation before visible light exposure. In an in vitro biofilm model, laser NIRT (980 nm) followed by exposure to PDI, showed a synergistic effect on bacterial viability loss (4-log CFU vs 1-log loss with individual treatments). Interestingly, pre-heating liquid medium had no significant impact on PDI efficacy, suggesting that both thermal and non-thermal effects of NIR may be involved. NIRT increased PS uptake, induced clefts in the biofilm matrix, and released bacterial cells from the biofilm. NIRT induced a transient increase in the temperature to 46°C of in vitro cultures, however under the same conditions, when mice were irradiated, skin temperature rose to 37°. Our findings suggest that NIR irradiation serves as a complementary treatment to PDI, allowing reducing PS concentration, and highlighting its potential as an effective and resource-efficient antibacterial approach.

10.1101/2024.05.08.593196

Cite

Citations (2)

Synthesis and cytotoxicity evaluation of olivacine-indole hybrids tethered by alkyl linkers

Natural Product Research (2021)

C Diez Mariela Céspedes Gabriela Di Venosa Gustavo Calvo Esteban Avigliano

In this work, eleven new derivatives were prepared of the alkaloid olivacine (1), which was isolated from the bark of Aspidosperma australe. These compounds (7a–k) are hybrids of olivacine and indoles or carbazole, tethered by alkyl chains of variable lengths (C-4, C-5 or C-6). Compounds 7a–k showed increased cytotoxicity towards a panel of four cell lines. The subcellular localization of olivacine and of the synthetic derivatives was studied by fluorescence microscopy. The cycles of K562 cells exposed to olivacine or compounds 7a–k were analysed by flow cytometry, and showed, for some of the new derivatives, a different profile of cell distribution among the phases of the cycle when compared to olivacine, which is indicative of lysosomal apoptosis.

Carbazole

K562 cells

10.1080/14786419.2021.1880401

Cite

Citations (2)

Cytotoxic effects of Argentinean plant extracts on tumour and normal cell lines.

PubMed (2011)

Leandro Mamone Gabriela Di Venosa J. J. Valla Laura Rodrı́guez Lautaro Gándara

In the search for possible new anti-cancer agents, we investigated the effects of 75 aqueous and methanol extracts from 41 Argentinean plant species. The effect in cell growth was evaluated in the LM2 mammary adenocarcinoma cells. In a second stage, the highly active selected extracts were assayed in 3 other tumour cell lines: melanoma B16, bladder MB49 and lung A549; and 3 normal cell lines: mammary Hb4a and keratinocytes PAM212 and HaCat. Eight methanol extracts were found to be highly cytotoxic: Collaea argentina leaf, Iochroma australe leaf, Ipomoea bonariensis flower, Jacaranda mimosifolia flower, Solanum amygdalifolium flower, Solanum chacoense leaf, Solanum sisymbriifolium flower and Solanum verbascifolium flower. However, extract inhibition on cell growth was highly dependent on cell type. In general, except for the highly resistant cell lines, the inhibitory concentrations 50% were in the range of 10-150 μg/ml The eight extracts highly inhibited cell growth in a concentration-dependent manner, and in general the methanol extracts were always more active than the aqueous. Murine cells appear to be more sensitive than human cells to the cytotoxic action of the plant extracts. The human melanoma B16 line was the most resistant to four of the extracts. In terms of selectivity, S. verbascifolium was the species which showed most selectivity for tumour cells. Overall, this is one of the first studies focusing on southern South American native plants and their biological effects. Since some species of 5 genera analyzed have been reported to possess different degrees of alkaloid content, we examined microtubule structures after extract treatments. The eight extracts induced destabilization, condensation and aggregation of microtubules in LM2 cells, although no depolarization, typical of Vinca alkaloids damage was observed. In a near future, antitumour activity of purified fractions of the extracts administered at non-toxic doses will be assayed in transplantable murine tumour models.

HaCaT

Solanum tuberosum

Source

Cite

Citations (13)

Mechanisms of Resistance to Photodynamic Therapy: An Update

Resistance to targeted anti-cancer therapeutics (2014)

Adriana Casas Christian Perotti Gabriela Di Venosa Alcira Batlle

Radioresistance

10.1007/978-3-319-12730-9_2

Cite

Citations (18)

In vitro photosensitisation of a murine mammary adenocarcinoma cell line with Verteporfin.

PubMed (2002)

Adriana Casas Gabriela Di Venosa Alcira Batlle Haydée Fukuda

Benzoporphyrin derivative monoacid ring A (BPD-MA) is a second generation hydrophobic photosensitiser for PDT that has been approved for ocular disease treatment. In the present paper we report the results of in vitro studies on the photosensitising activity of Verteporfin (liposomally formulated BPD-MA) using an adenocarcinoma derived cell line. Our findings show a quick and efficient uptake of Verteporfin by LM3 cells, reaching maxima concentrations after 5 hr exposure to 18 microg Verteporfin/ml. Independently on the concentration, plateau levels are attained 5 hr after exposure to Verteporfin. Exposure of the cells to the photosensitiser appears to be safe in the darkness within a broad range of concentrations. The hydroxyl radical scavenger mannitol afforded the highest protection against PDT, while L-tryptophan, a well known and efficient singlet oxygen quencher was not an effective protector at all, showing scavenging activity only when it was supplemented at concentration as high as 10 mM and when 50% of the cells were affected, showing that in addition to singlet oxygen, which is considered the primary cytotoxic agent in PDT, other interconvertible reactive oxygen specie (ROS), in particular HO are also generated. Verteporfin-PDT also induced morphological features typical of apoptotic cells. Results of the present work show that the LM3 adenocarcinoma cell can be effectively sensitised with Verteporfin-PDT.

Verteporfin

Source

Cite

Citations (5)

Ras-transfected human mammary tumour cells are resistant to photodynamic therapy by mechanisms related to cell adhesion

Life Sciences (2022)

Lorena Rodríguez Gabriela Di Venosa Martín A. Rivas Ángeles Juarranz Francisco Sanz‐Rodríguez

Photodynamic therapy (PDT) is a treatment modality for several cancers involving the administration of a tumour-localising photosensitiser (PS) and its subsequent activation by light, resulting in tumour damage. Ras oncogenes have been strongly associated with chemo- and radio-resistance. Based on the described roles of adhesion and cell morphology on drug resistance, we studied if the differences in shape, cell-extracellular matrix and cell-cell adhesion induced by Ras transfection, play a role in the resistance to PDT.We employed the human normal breast HB4a cells transfected with H-RAS and a panel of five PSs.We found that resistance to PDT of the HB4a-Ras cells employing all the PSs, increased between 1.3 and 2.5-fold as compared to the parental cells. There was no correlation between resistance and intracellular PS levels or PS intracellular localisation. Even when Ras-transfected cells present lower adherence to the ECM proteins, this does not make them more sensitive to PDT or chemotherapy. On the contrary, a marked gain of resistance to PDT was observed in floating cells as compared to adhesive cells, accounting for the higher ability conferred by Ras to survive in conditions of decreased cell-extracellular matrix interactions. HB4a-Ras cells displayed disorganisation of actin fibres, mislocalised E-cadherin and vinculin and lower expression of E-cadherin and β1-integrin as compared to HB4a cells.Knowledge of the mechanisms of resistance to photodamage in Ras-overexpressing cells may lead to the optimization of the combination of PDT with other treatments.

Vinculin

10.1016/j.lfs.2022.121287

Cite

Citations (2)