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Métodos Terapêuticos e Terapias MTCI
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1.
Sci Rep ; 10(1): 2838, 2020 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-32071352

RESUMO

A major obstacle to nanodrugs-mediated cancer therapy is their rapid uptake by the reticuloendothelial system that decreases the systemic exposure of the nanodrugs to tumors and also increases toxicities. Intralipid has been shown to reduce nano-oxaliplatin-mediated toxicity while improving bioavailability. Here, we have found that Intralipid reduces the cytotoxicity of paclitaxel for human monocytic cells, but not for breast, lung, or pancreatic cancer cells. Intralipid also promotes the polarization of macrophages to the anti-cancer M1-like phenotype. Using a xenograft breast cancer mouse model, we have found that Intralipid pre-treatment significantly increases the amount of paclitaxel reaching the tumor and promotes tumor apoptosis. The combination of Intralipid with half the standard clinical dose of Abraxane reduces the tumor growth rate as effectively as the standard clinical dose. Our findings suggest that pre-treatment of Intralipid has the potential to be a powerful agent to enhance the tumor cytotoxic effects of Abraxane and to reduce its off-target toxicities.


Assuntos
Paclitaxel Ligado a Albumina/farmacologia , Neoplasias da Mama/tratamento farmacológico , Imunidade Inata/efeitos dos fármacos , Fosfolipídeos/farmacologia , Óleo de Soja/farmacologia , Animais , Antineoplásicos , Apoptose/efeitos dos fármacos , Disponibilidade Biológica , Neoplasias da Mama/imunologia , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Emulsões/farmacologia , Feminino , Xenoenxertos , Humanos , Camundongos , Nanopartículas/química , Oxaliplatina/farmacologia , Paclitaxel/química , Paclitaxel/farmacologia , Fosfolipídeos/imunologia , Óleo de Soja/imunologia , Ensaios Antitumorais Modelo de Xenoenxerto
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