Analysis of sono-photodynamic effects with PpIX - in Vitro and in vivo studies
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Tipo de documento: | Dissertação |
Idioma: | eng |
Título da fonte: | Biblioteca Digital de Teses e Dissertações da USP |
Texto Completo: | https://www.teses.usp.br/teses/disponiveis/76/76134/tde-08102020-101551/ |
Resumo: | 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 (kSPD ≅ kSD + 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. |
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Analysis of sono-photodynamic effects with PpIX - in Vitro and in vivo studiesAnálise dos efeitos sono-fotodinâmicos com PpIX - estudos in vitro e in vivoAnálise EspectroscópicaNecrose fígado de ratoPhotodynamic therapyProtoporfirina IXProtoporphyrin IXRat liver necrosisSonodynamic therapySpectroscopy analysisTerapia fotodinâmicaTerapia sonodinâmicaSono-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 (kSPD ≅ kSD + 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.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 (kSPD ≅ kSD + 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.Biblioteca Digitais de Teses e Dissertações da USPPratavieira, SebastiãoAyala, Erika Toneth Ponce2020-08-12info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttps://www.teses.usp.br/teses/disponiveis/76/76134/tde-08102020-101551/reponame:Biblioteca Digital de Teses e Dissertações da USPinstname:Universidade de São Paulo (USP)instacron:USPLiberar o conteúdo para acesso público.info:eu-repo/semantics/openAccesseng2024-08-22T22:29:03Zoai:teses.usp.br:tde-08102020-101551Biblioteca Digital de Teses e Dissertaçõeshttp://www.teses.usp.br/PUBhttp://www.teses.usp.br/cgi-bin/mtd2br.plvirginia@if.usp.br|| atendimento@aguia.usp.br||virginia@if.usp.bropendoar:27212024-08-22T22:29:03Biblioteca Digital de Teses e Dissertações da USP - Universidade de São Paulo (USP)false |
dc.title.none.fl_str_mv |
Analysis of sono-photodynamic effects with PpIX - in Vitro and in vivo studies Análise dos efeitos sono-fotodinâmicos com PpIX - estudos in vitro e in vivo |
title |
Analysis of sono-photodynamic effects with PpIX - in Vitro and in vivo studies |
spellingShingle |
Analysis of sono-photodynamic effects with PpIX - in Vitro and in vivo studies Ayala, Erika Toneth Ponce Análise Espectroscópica Necrose fígado de rato Photodynamic therapy Protoporfirina IX Protoporphyrin IX Rat liver necrosis Sonodynamic therapy Spectroscopy analysis Terapia fotodinâmica Terapia sonodinâmica |
title_short |
Analysis of sono-photodynamic effects with PpIX - in Vitro and in vivo studies |
title_full |
Analysis of sono-photodynamic effects with PpIX - in Vitro and in vivo studies |
title_fullStr |
Analysis of sono-photodynamic effects with PpIX - in Vitro and in vivo studies |
title_full_unstemmed |
Analysis of sono-photodynamic effects with PpIX - in Vitro and in vivo studies |
title_sort |
Analysis of sono-photodynamic effects with PpIX - in Vitro and in vivo studies |
author |
Ayala, Erika Toneth Ponce |
author_facet |
Ayala, Erika Toneth Ponce |
author_role |
author |
dc.contributor.none.fl_str_mv |
Pratavieira, Sebastião |
dc.contributor.author.fl_str_mv |
Ayala, Erika Toneth Ponce |
dc.subject.por.fl_str_mv |
Análise Espectroscópica Necrose fígado de rato Photodynamic therapy Protoporfirina IX Protoporphyrin IX Rat liver necrosis Sonodynamic therapy Spectroscopy analysis Terapia fotodinâmica Terapia sonodinâmica |
topic |
Análise Espectroscópica Necrose fígado de rato Photodynamic therapy Protoporfirina IX Protoporphyrin IX Rat liver necrosis Sonodynamic therapy Spectroscopy analysis Terapia fotodinâmica Terapia sonodinâmica |
description |
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 (kSPD ≅ kSD + 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. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020-08-12 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://www.teses.usp.br/teses/disponiveis/76/76134/tde-08102020-101551/ |
url |
https://www.teses.usp.br/teses/disponiveis/76/76134/tde-08102020-101551/ |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
|
dc.rights.driver.fl_str_mv |
Liberar o conteúdo para acesso público. info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Liberar o conteúdo para acesso público. |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.coverage.none.fl_str_mv |
|
dc.publisher.none.fl_str_mv |
Biblioteca Digitais de Teses e Dissertações da USP |
publisher.none.fl_str_mv |
Biblioteca Digitais de Teses e Dissertações da USP |
dc.source.none.fl_str_mv |
reponame:Biblioteca Digital de Teses e Dissertações da USP instname:Universidade de São Paulo (USP) instacron:USP |
instname_str |
Universidade de São Paulo (USP) |
instacron_str |
USP |
institution |
USP |
reponame_str |
Biblioteca Digital de Teses e Dissertações da USP |
collection |
Biblioteca Digital de Teses e Dissertações da USP |
repository.name.fl_str_mv |
Biblioteca Digital de Teses e Dissertações da USP - Universidade de São Paulo (USP) |
repository.mail.fl_str_mv |
virginia@if.usp.br|| atendimento@aguia.usp.br||virginia@if.usp.br |
_version_ |
1809090526855561216 |