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EGFR-targeted immunoliposomes efficiently deliver docetaxel to prostate cancer cells

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Eloy, Josimar O. ; Ruiz, Amalia ; de Lima, Felipe Tita ; Petrilli, Raquel ; Raspantini, Giovanni ; Barros Nogueira, Karina Alexandre ; Santos, Elias ; de Oliveira, Carlos Sabino ; Borges, Julio Cesar ; Marchetti, Juliana Maldonado ; Al-Jamal, Wafa T. ; Chorilli, Marlus
Número total de Autores: 12
Tipo de documento: Artigo Científico
Fonte: COLLOIDS AND SURFACES B-BIOINTERFACES; v. 194, p. 12-pg., 2020-10-01.
Resumo

Prostate cancer is the second cause of cancer death in men worldwide. Docetaxel (DTX), an antimitotic drug, is widely used for the treatment of metastatic prostate cancer patients. Taxotere (R) is a commercial DTX formulation. It contains a polysorbate 80 surfactant to improve DTX aqueous solubility, which has been associated with hypersensitivity reactions in patients. Liposomes have been used as promising delivery systems for a range of hydrophobic drugs, such as DTX, offering improved drug water solubility and biocompatibility, without compromising its anticancer activity. Herein, DTX-loaded liposomes were developed using the Box-Behnken factorial design. The optimized formulation was nano-sized, homogenous in size (67.47 nm) with high DTX encapsulation efficiency (99.95 %). The encapsulated DTX was in a soluble amorphous state, which was slowly released. Next, to increase the liposomes selectivity to prostate cancer cells, cetuximab, an anti-EGFR monoclonal antibody. was successfully conjugated to the surface of liposomes, without compromising cetuximab protein structure and stability. As expected, our results showed higher cellular uptake and toxicity of immunoliposomes, compared to non-targeted liposomes, in DU145 (EGFR-overxpressing) prostate cancer cells. To the best of our knowledge, this is the first report of engineering EGFR-targeted liposomes to enhance the selectivity of DTX delivery to EGFRpositive prostate cancer cells. (AU)

Processo FAPESP: 18/21104-2 - Imunolipossomas contendo Docetaxel: efeito in vitro em esferoides multicelulares de tumores em 3D de cultura celular de câncer de próstata
Beneficiário:Felipe Tita de Lima
Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Iniciação Científica
Processo FAPESP: 18/00814-1 - Desenvolvimento e caracterização de lipossomas e imunolipossomas liofilizados contendo docetaxel para potencial aplicação no tratamento do câncer de próstata
Beneficiário:Felipe Tita de Lima
Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
Processo FAPESP: 17/04091-1 - Desenvolvimento e caracterização de sistemas de liberação contendo docetaxel para a otimização da terapia do câncer de próstata: imunolipossomas e nanopartículas poliméricas
Beneficiário:Juliana Maldonado Marchetti
Modalidade de apoio: Auxílio à Pesquisa - Regular
Processo FAPESP: 16/02723-8 - Lipossomas contendo docetaxel funcionalizados com cetuximabe em combinação com a terapia plasmônica com nanobastões de ouro para o tratamento do câncer de próstata
Beneficiário:Josimar de Oliveira Eloy
Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado