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Projeto de investigação
Inference of DNA damage for Phototherapy Applications
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Liposomes encapsulating DNA-intercalating molecules: an approach for Photodynamic Therapy application
Publication . Pivetta, Thais Priscilla; Raposo, Maria de Fátima; Ribeiro, Paulo
Photodynamic Therapy (PDT) has been widely explored for the treatment of some types of cancer as a selective and minimally invasive therapy, making use of photosensitizers (PS) that in presence of oxy-gen and light produce reactive oxygen species and consequent cell death. Many molecules have been investigated regarding the photosensitizing potential, however, most of the PS present some drawbacks such as aggregation and low solubility in physiological environments influencing the efficacy. The use of nanostructures for the PS molecules encapsulation has been addressed by means of lipid nanostruc-tures that are biocompatible and biodegradable. Liposomes are lipid-based vesicles able to encapsulate both hydrophilic and hydrophobic drugs and are promising alternatives to enhance the therapy efficacy. The main goal of this work was to select non-conventional photosensitizers among some DNA-interca-lating molecules, followed by the encapsulation of these molecules aiming the PDT application in skin cancer cells. For this purpose, the phototoxic potential of a set of DNA-intercalating molecules was investigated. Results revealed that Methylene Blue (MB) and Acridine Orange (AO) molecules present the most significant phototoxic effects in a skin cancer cell line. Liposome’s stability has also been evaluated, and the most promising formulations were able to provide higher stability for the encapsula-tion of the MB and AO photosensitizers which also revealed, in general, higher encapsulation efficiency. Phototoxicity was shown not to be significantly affected by PS encapsulation however, different effects on the size and encapsulation efficiency were observed for MB and AO. Langmuir monolayer studies unveiled the effect of the selected molecules on the lipid’s interaction with results suggesting that MB and AO cause a decrease in the monolayer order and consequently increasing the membrane elasticity. In summary, MB-liposomes has cytotoxic potential for cancer cells while AO-liposomes presents pho-totoxic potential at very low concentrations. These results are important to comprehend the possible application of these systems for skin cancer photodynamic therapy.
The Effect of UV-Vis Radiation on DNA Systems Containing the Photosensitizers Methylene Blue and Acridine Orange
Publication . Pivetta, Thais P.; Ribeiro, Paulo A.; Raposo, Maria; DF – Departamento de Física; CeFITec – Centro de Física e Investigação Tecnológica; LIBPhys-UNL; MDPI - Multidisciplinary Digital Publishing Institute
As a vital biomolecule, DNA is known as a target of antineoplastic drugs for cancer therapy. These drugs can show different modes of interaction with DNA, with intercalation and groove binding being the most common types. The intercalation of anticancer drugs with DNA can lead to the disruption of its normal function, influencing cell proliferation. Methylene blue (MB) and acridine orange (AO) are examples of DNA-intercalating agents that have been studied for their application against some types of cancer, mainly for photodynamic therapy. In this work, the impact of light irradiation on these compounds in the absence and presence of DNA was analyzed by means of UV-vis spectroscopy. Bathochromic and hypochromic shifts were observed in the absorbance spectra, revealing the intercalation of the dyes with the DNA base pairs. Dyes with and without DNA present different profiles of photodegradation, whereby the dyes alone were more susceptible to degradation. This can be justified by the intercalation of the dyes on the DNA base pairs allowing the DNA molecule to partially hinder the molecules’ exposition and, therefore, reducing their degradation.
Nanoparticle systems for cancer phototherapy
Publication . Pivetta, Thais P.; Botteon, Caroline E. A.; Ribeiro, Paulo A.; Marcato, Priscyla D.; Raposo, Maria; DF – Departamento de Física; CeFITec – Centro de Física e Investigação Tecnológica; LIBPhys-UNL; MDPI AG
Photodynamic therapy (PDT) and photothermal therapy (PTT) are photo-mediated treatments with different mechanisms of action that can be addressed for cancer treatment. Both phototherapies are highly successful and barely or non-invasive types of treatment that have gained attention in the past few years. The death of cancer cells because of the application of these therapies is caused by the formation of reactive oxygen species, that leads to oxidative stress for the case of photodynamic therapy and the generation of heat for the case of photothermal therapies. The advancement of nanotechnology allowed significant benefit to these therapies using nanoparticles, allowing both tuning of the process and an increase of effectiveness. The encapsulation of drugs, development of the most different organic and inorganic nanoparticles as well as the possibility of surfaces’ functionalization are some strategies used to combine phototherapy and nanotechnology, with the aim of an effective treatment with minimal side effects. This article presents an overview on the use of nanostructures in association with phototherapy, in the view of cancer treatment.
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Fundação para a Ciência e a Tecnologia
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OE
Número da atribuição
PD/BD/142829/2018