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Master's Dissertation
DOI
https://doi.org/10.11606/D.76.2020.tde-08102020-101551
Document
Author
Full name
Erika Toneth Ponce Ayala
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Carlos, 2020
Supervisor
Committee
Pratavieira, Sebastião (President)
Pavan, Théo Zeferino
Zezell, Denise Maria
Title in English
Analysis of sono-photodynamic effects with PpIX - in Vitro and in vivo studies
Keywords in English
Photodynamic therapy
Protoporphyrin IX
Rat liver necrosis
Sonodynamic therapy
Spectroscopy analysis
Abstract in English
Sono-photodynamic therapy (SPDT) is a relatively new and promising approach to cancer treatment, based on the combination of an sono-photoactive drug, low-intensity ultrasound and light. This combined therapy increases anticancer effects by the induction of cell death into deeper body regions. This study aims to analyze the mechanisms and effects of the sono-photodynamic (SPD) action on Protoporphyrin IX (PpIX) solutions and PpIX-loaded rat healthy liver. In vitro, PpIX 5μM solutions were irradiated with light (635 nm, 30-50 mW/cm2) (photodynamic (PD) action), ultrasound (1MHz, 1-2 W/cm2) (sonodynamic(SD) action) and the combination of both sources. This combination was carried out in three different ways: applying both sources simultaneously (SPD action) and applying one source after the other (PD+SD and SD+PD action). The absorption spectra of PpIX solutions recorded during irradiation, showed that the PpIX decay rate (k) induced by SPD action was approximately the sum of those induced by the PD and SD action (kSPDkSD + kPD). In vivo, rats were intraperitoneal injected with 5-aminolevulinic acid (ALA) at doses of 500 mg/kg body weigh to load the rat liver with higher concentration of PpIX. At 3h (time of optimum drug concentration in the liver) after injection, the PpIX-loaded livers were irradiated with light (635 nm, 180 ± 9 J/cm2) (PD action), ultrasound (1.0 MHz, 765 ± 38 J/cm2) (SD action), and the combination of both sources (SPD, PD+SD, SD+PD action). For these procedures, a single probe capable of irradiating light and ultrasound simultaneously was built. After 30 hours, animals were sacrificed, the livers were surgically removed and analyzed through scanned histological slides. The SPD and PD+SD action induced greater necrosis depth than either PD or SD action. These results suggested that the combined action could improve the drug decay rate, as well as having a greater scope than either PD or SD action, but it certainly must be more widely studied.
Title in Portuguese
Análise dos efeitos sono-fotodinâmicos com PpIX - estudos in vitro e in vivo
Keywords in Portuguese
Análise Espectroscópica
Necrose fígado de rato
Protoporfirina IX
Terapia fotodinâmica
Terapia sonodinâmica
Abstract in Portuguese
A terapia sonofotodinâmica (TSFD) é uma abordagem relativamente nova e promissora para o tratamento do câncer, baseada na combinação de uma droga sono-fotoativa, ultrassom de baixa intensidade e luz. Esta terapia combinada aumenta os efeitos anticâncer pela indução da morte celular em regiões mais profundas do corpo. Este estudo tem como objetivo analisar os mecanismos e efeitos da ação sono-fotodinâmica (SFD) em soluções de Protoporfirina IX (PpIX) e em fígado de rato saudável na presença de PpIX. In vitro, as soluções PpIX 5μM foram irradiadas com luz (635 nm, 30-50 mW/cm2) (ação fotodinâmica (FD)), ultrassom (1 MHz, 1-2 W/cm2) (ação sonodinâmica (SD)) e a combinação de ambas as fontes. Esta combinação foi realizada de três maneiras diferentes: aplicando ambas as fontes simultaneamente (ação SFD) e aplicando uma fonte após a outra (ação FD+SD e ação SD+FD). Os espectros de absorção das soluções da PpIX registrados durante a irradiação, mostraram que a taxa de decaimento de PpIX (k) induzida pela ação SFD foi aproximadamente a soma daquelas induzidas pela ação FD e SD (kSPDkSD + kPD). In vivo, os ratos foram injetados por via intraperitoneal com 5-aminolevulínico (ALA) em doses de 500 mg/kg do peso corporal. Após 3 horas da injeção (tempo para a concentração ideal do fármaco no fígado), os fígados carregados com PpIX foram irradiados com luz (635 nm, 180 ± 9 J/cm2) (ação FD), ultrassom (1,0 MHz, 765 ± 38 J/cm2) (ação SD) e a combinação de ambas as fontes (ação SFD, FD+SD, SD+FD). Para esses procedimentos, foi construída uma única sonda capaz de irradiar luz e ultrassom simultaneamente. Após 30 horas, os animais foram sacrificados, os fígados foram removidos cirurgicamente e analisados através de lâminas histológicas digitalizadas. A ação SFD e FD+SD induziram maior profundidade de necrose do que a ação FD ou SD. Esses resultados sugerem que a ação combinada pode melhorar a taxa de degradação da droga utilizada como sensibilizador, além de ter um escopo maior do que a ação PD ou SD, mas certamente deve ser mais amplamente estudada.
 
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Publishing Date
2020-10-20
 
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