Iron oxide polyaniline-coated nanoparticles modulate tumor microenvironment in breast cancer: an in vitro study on the reprogramming of tumor-associated macrophages

Cancer Nanotechnology

Research

Eneida Santos de Oliveira¹  Anna Carolina Pinheiro Lage²  Camila Sales Nascimento³  Naiara Clemente Tavares³  Rodrigo Corrêa-Oliveira³  Érica Alessandra Rocha Alves³  Carlos Eduardo Calzavara-Silva³  Mônica Maria Magalhães Caetano³  Izabella Cristina Andrade Batista³  Celso Pinto de Melo⁴  Stella Garcia Colombarolli⁵ 

[1] Gerência da Rede Ambulatorial Especializada, Secretaria Municipal de Saúde de Belo Horizonte, Prefeitura de Belo Horizonte, 2336 Afonso Pena Avenue, 301300-007, Belo Horizonte, Brazil;Grupo de Biotecnologia Aplicada ao Estudo de Patógenos, Instituto René Rachou, Fiocruz Minas, Av. Augusto de Lima, 1715 –Barro Preto, 30190-002, Belo Horizonte, MG, Brazil;Grupo de Pesquisa em Imunologia Celular e Molecular, Instituto René Rachou, Fiocruz Minas, Av. Augusto de Lima, 1715, Barro Preto, 30190-002, Belo Horizonte, MG, Brazil;Grupo de Polímeros Não-Convencionais, Departamento de Física, Universidade Federal de Pernambuco, Av. Prof. Moraes Rego, 1235, Cidade Universitária, 50670-901, Recife, PE, Brazil;Istituto di Scienze e Tecnologie Chimiche (SCITEC-CNR), National Research Council of Italy, Roma, Italy;

关键词: Breast cancer;    Tumor-associated macrophages (TAMs);    Macrophages;    Polarization;    Iron oxide nanoparticles;    Tumor microenvironment;    Immunotherapy;    Nanotechnology;   

DOI  :  10.1186/s12645-023-00225-3

 received in 2023-07-03, accepted in 2023-08-28,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundBreast cancer is the neoplastic disease with the highest incidence and mortality in the female population worldwide. Treatment remains challenging due to various factors. Therefore, it is of great importance to develop new therapeutic strategies that promote the safe destruction of neoplastic cells without compromising patients' quality of life. Among advances in the treatment of breast cancer, immunotherapy stands out as a promising trend. Recent studies have demonstrated the potential of iron oxide nanoparticles in promoting the reprogramming of M2 macrophages (pro-tumor phenotype) into M1 macrophages (anti-tumor phenotype) within the tumor microenvironment, resulting in potent antitumor effects. In this study, the effect of polyaniline-coated iron oxide nanoparticles (Pani/y-Fe2O3) on macrophage polarization and breast cancer cell death was investigated.MethodsThe non-cytotoxic concentration of nanoparticles was determined using the MTT assay. For in vitro co-culture experiments, breast cancer cell lines MCF -7 and MDA-MB -231 and macrophages THP-1 were co-cultured in a Transwell system and then the effects of Pani/y-Fe2O3 on cell viability, gene expression, cytokine profile, and oxidative stress markers were investigated.ResultsThe results showed that Pani/y-Fe2O3 nanoparticles induced M2-to-M1 macrophage polarization in both cell lines through different pathways. In MCF -7 and THP-1 macrophage co-culture, the study showed a decrease in cytokine levels IL -1β, upregulation of M1-associated genes (IL-12, TNF-α) in macrophages, resulting in increased MCF -7 cell death by apoptosis (caspase 3/7+). In MDA-MB -231 co-cultures, increases in cytokines IL -6, IL -1β, and oxidative stress markers were observed, as well as upregulation of the inducible nitric oxide synthase (iNOS) gene in macrophages, leading to tumor cell death via apoptosis-independent pathways (Sytox+).ConclusionsThese findings highlight the potential of Pani/y-Fe2O3 as a promising therapeutic approach in the context of breast cancer treatment by effectively reprogramming M2 macrophages into an anti-tumor M1 phenotype, Pani/y-Fe2O3 nanoparticles demonstrated the ability to elicit antitumor effects in both MCF-7 and MDA-MB-231 breast cancer cell lines.

【 授权许可】

CC BY   
© Springer-Verlag GmbH Austria, part of Springer Nature 2023

【 图 表 】

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