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Nanomedicine ; 11(8): 1961-70, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26238076

RESUMO

This study represents a novel approach for intraoperative ovarian cancer treatment based on the combinatorial effect of a targeted photodynamic therapy (PDT) associated with suppression of the DJ-1 protein, one of the key players in the ROS defense of cancer cells. To assess the potential of the developed therapy, dendrimer-based nanoplatforms for cancer-targeted delivery of near-infrared photosensitizer, phthalocyanine, and DJ-1 siRNA have been constructed. In vitro studies revealed that therapeutic efficacy of the combinatorial approach was enhanced when compared to PDT alone and this enhancement was more pronounced in ovarian carcinoma cells, which are characterized by higher basal levels of DJ-1 protein. Moreover, the ovarian cancer tumors exposed to a single dose of combinatorial therapy were completely eradicated from the mice and the treated animals showed no evidence of cancer recurrence. Thus, the developed therapeutic approach can be potentially employed intraoperatively to eradicate unresactable cancer cells. FROM THE CLINICAL EDITOR: The complete clearance of microscopic residual tumor cells during excision surgery is important to improve survival of the patient. In this interesting paper, the authors developed a novel approach using targeted photodynamic therapy (PDT), combining a photosensitizer, phthalocyanine, and DJ-1 siRNA for the treatment of ovarian cancer. The data showed that this approach increased cancer cell killing and may pave way for future clinical studies.


Assuntos
Indóis/uso terapêutico , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteínas Oncogênicas/genética , Neoplasias Ovarianas/terapia , Fármacos Fotossensibilizantes/uso terapêutico , RNA Interferente Pequeno/uso terapêutico , Animais , Linhagem Celular Tumoral , Dendrímeros/química , Dendrímeros/metabolismo , Portadores de Fármacos/química , Portadores de Fármacos/metabolismo , Sistemas de Liberação de Medicamentos , Feminino , Humanos , Indóis/administração & dosagem , Isoindóis , Camundongos , Camundongos Nus , Nanoestruturas/química , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Ovário/metabolismo , Ovário/patologia , Fotoquimioterapia , Fármacos Fotossensibilizantes/administração & dosagem , Proteína Desglicase DJ-1 , RNA Interferente Pequeno/administração & dosagem , Terapêutica com RNAi , Espécies Reativas de Oxigênio/metabolismo
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