聚苯胺包被氧化铁纳米粒子重新编程肿瘤相关巨噬细胞以治疗乳腺癌。
Reprogramming of tumor-associated macrophages by polyaniline-coated iron oxide nanoparticles applied to treatment of breast cancer.
发表日期:2023 Mar 17
作者:
Camila Nascimento, Flávia Castro, Mariana Domingues, Anna Lage, Érica Alves, Rodrigo de Oliveira, Celso de Melo, Carlos Eduardo Calzavara-Silva, Bruno Sarmento
来源:
Disease Models & Mechanisms
摘要:
乳腺癌是全球女性人群最常见的癌症类型。这是一种高发病率和地理分布广泛的疾病,对全球公共卫生产生了负面影响,并且影响了癌症患者的生活质量。在新的方法中,癌症免疫治疗是肿瘤学中最有前途的趋势,它通过刺激宿主自身的免疫系统来有效地销毁癌细胞。最近的证据表明,氧化铁纳米颗粒可以促进M2向M1巨噬细胞的重编程,具有抗肿瘤效果。因此,本研究旨在评估聚苯胺涂覆的磁赤铁矿(Pani/γ-Fe2O3)纳米颗粒调节2D单层和3D多细胞乳腺癌模型中人类巨噬细胞的能力。观察到Pani/γ-Fe2O3纳米颗粒可以将IL-10刺激的巨噬细胞改变为促炎症谱系,降低CD163+的比例并增加2D模型中的CD86+比例。纳米颗粒成功被摄取到3D模型中的巨噬细胞中,并且还能够在三重MCTs模型中增加它们的CD86+比例。总的来说,我们的发现为使用Pani/γ-Fe2O3纳米颗粒作为免疫调节疗法重新编程巨噬细胞至抗肿瘤M1表型开辟了新的视角,为乳腺癌免疫治疗提供了新的工具。版权所有©2023作者。由Elsevier B.V.出版。保留所有权利。
Breast cancer is the most commonly diagnosed type of cancer among the female population worldwide. It is a disease with a high incidence and geographic distribution that negatively impacts global public health and deleteriously affect the quality of life of cancer patients. Among the new approaches, cancer immunotherapy is the most promising trend in oncology by stimulating the host's own immune system to efficiently destroy cancer cells. Recent evidence has indicated that iron oxide nanoparticles can promote the reprograming of M2 into M1 macrophages with anti-tumor effects in the tumor microenvironment. Thus, the aim of the present work was to evaluate the ability of polyaniline-coated maghemite (Pani/γ-Fe2O3) nanoparticles to modulate human macrophages in 2D monolayers and 3D multicellular breast cancer models. It was observed that Pani/γ-Fe2O3 NPs re-educated IL-10-stimulated macrophages towards a pro-inflammatory profile, decreasing the proportion of CD163+ and increasing the CD86+ proportion in 2D models. NPs were successfully taken-up by macrophages presented in the 3D model and were also able to induce an increasing in their CD86+ proportion in triple MCTs model. Overall, our findings open new perspectives on the use of Pani/γ-Fe2O3 NPs as an immunomodulatory therapy for macrophage reprogramming towards an anti-tumor M1 phenotype, providing a new tool for breast cancer immunotherapies.Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.