Meng Xiang,1,* Chengzhi Chen,2,* Yuting Chen,1,* Yuhan Zhang,1 Lei Shi,1 Yan Chen,1 Jie Li,2 Bowen Li,1 Bin Zeng,2 H Rosie Xing,1 Jianyu Wang,2 Zhen Zou2 

1State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 2Molecular Biology Laboratory of Respiratory Disease, Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Zhen Zou; Jianyu Wang, Email zouzhen@cqmu.edu.cn; 102758@cqmu.edu.cn

Introduction: Inhalation exposure to silica nanoparticles (SiNPs) is frequently inevitable in modern times. Although the impact of SiNPs on the ecological niche of the lungs has been extensively explored, the role and mechanism of SiNPs in the microenvironment of lung tumors remain elusive.
Methods: In this investigation, Lewis lung carcinoma (LLC) was implanted into the left lung in situ after 28 days of intratracheal SiNPs injection into the lungs of mice. This study evaluates the effects of SiNPs on the tumor immune microenvironment both in vitro and in vivo. Our findings indicate that SiNPs can suppress lung cancer by modulating the immune microenvironment of tumors.
Results: SiNPs treatment promotes macrophage M1 polarization by activating both NF-κB pathway and glycolytic mechanisms. This phenomenon may be associated with lung inflammation and fluctuation in the pre-metastatic and metastatic microenvironments induced by SiNPs exposure in mice. Additionally, we have shown for the first time that SiNPs have an inhibitory effect on lung carcinogenesis and its progression.
Conclusion: This study uniquely demonstrates that SiNPs suppress lung cancer by promoting M1 polarization of macrophages in the immune microenvironment of lung tumors. Our findings are critical in exploring the interaction between SiNPs and lung cancer.

Keywords: silicon nanoparticles, lung cancer, macrophage polarization, NF-κB, glycolysis