Nascimento Camila, Castro Flávia, Domingues Mariana, Lage Anna, Alves Érica, de Oliveira Rodrigo, de Melo Celso, Eduardo Calzavara-Silva Carlos, Sarmento Bruno
Grupo de Pesquisa em Imunologia Celular e Molecular, Instituto René Rachou - Fiocruz Minas, Av. Augusto de Lima, 1715 - Barro Preto, Belo Horizonte, MG 30190-002, Brazil.
INEB - Instituto Nacional de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal; i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal.
Int J Pharm. 2023 Apr 5;636:122866. doi: 10.1016/j.ijpharm.2023.122866. Epub 2023 Mar 18.
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-FeO) nanoparticles to modulate human macrophages in 2D monolayers and 3D multicellular breast cancer models. It was observed that Pani/γ-FeO 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-FeO NPs as an immunomodulatory therapy for macrophage reprogramming towards an anti-tumor M1 phenotype, providing a new tool for breast cancer immunotherapies.
乳腺癌是全球女性群体中最常被诊断出的癌症类型。它是一种发病率高且分布广泛的疾病，对全球公共卫生产生负面影响，并严重影响癌症患者的生活质量。在新的治疗方法中，癌症免疫疗法通过刺激宿主自身免疫系统有效破坏癌细胞，是肿瘤学中最具前景的趋势。最近的证据表明，氧化铁纳米颗粒可促进肿瘤微环境中M2巨噬细胞重编程为具有抗肿瘤作用的M1巨噬细胞。因此，本研究的目的是评估聚苯胺包覆磁赤铁矿（Pani/γ-FeO）纳米颗粒在二维单层和三维多细胞乳腺癌模型中调节人巨噬细胞的能力。研究发现，在二维模型中，Pani/γ-FeO纳米颗粒将白细胞介素-10刺激的巨噬细胞重新诱导为促炎表型，降低了CD163的比例，增加了CD86的比例。纳米颗粒成功被三维模型中的巨噬细胞摄取，并且在三阴性乳腺癌模型中也能够使其CD86比例增加。总体而言，我们的研究结果为使用Pani/γ-FeO纳米颗粒作为免疫调节疗法使巨噬细胞重编程为抗肿瘤M1表型开辟了新的前景，为乳腺癌免疫治疗提供了一种新工具。
