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

• 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