β-D-Glucose-Reduced Silver Nanoparticles Remodel the Tumor Microenvironment in a Murine Model of Triple-Negative Breast Cancer

β-D-葡萄糖还原的银纳米颗粒可重塑三阴性乳腺癌小鼠模型中的肿瘤微环境

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作者:Pedro Félix-Piña,Moisés Armides Franco Molina,Paola Leonor García Coronado,Heriberto Prado-Garcia,Diana Ginette Zarate-Triviño,Beatriz Elena Castro-Valenzuela,Kenia Arisbe Moreno-Amador,Ashanti Concepción Uscanga Palomeque,Cristina Rodríguez Padilla

Abstract

Breast cancer is the most diagnosed type of cancer worldwide and the second cause of death in women. Triple-negative breast cancer (TNBC) is the most aggressive, and due to the lack of specific targets, it is considered the most challenging subtype to treat and the subtype with the worst prognosis. The present study aims to determine the antitumor effect of beta-D-glucose-reduced silver nanoparticles (AgNPs-G) in a murine model of TNBC, as well as to study its effect on the tumor microenvironment. In an airbag model with 4T1 tumor cell implantation, the administration of AgNPs-G or doxorubicin showed antitumoral activity. Using immunohistochemistry it was demonstrated that treatment with AgNPs-G decreased the expression of PCNA, IDO, and GAL-3 and increased the expression of Caspase-3. In the tumor microenvironment, the treatment increased the percentage of memory T cells and innate effector cells and decreased CD4+ cells and regulatory T cells. There was also an increase in the levels of TNF-α, IFN-γ, and IL-6, while TNF-α was increased in serum. In conclusion, we suggest that AgNPs-G treatment has an antitumor effect that is demonstrated by its ability to remodel the tumor microenvironment in mice with TNBC.

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