Unexpected Inhibitory Role of Silica Nanoparticles on Lung Cancer Development by Promoting M1 Polarization of Macrophages

Int J Nanomedicine. 2024 Nov 1:19:11087-11104. doi: 10.2147/IJN.S472796. eCollection 2024.

Abstract

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: NF-κB; glycolysis; lung cancer; macrophage polarization; silicon nanoparticles.

MeSH terms

  • Animals
  • Carcinoma, Lewis Lung* / pathology
  • Cell Line, Tumor
  • Lung Neoplasms* / chemically induced
  • Macrophage Activation / drug effects
  • Macrophages* / drug effects
  • Mice
  • Mice, Inbred C57BL*
  • NF-kappa B / metabolism
  • Nanoparticles* / chemistry
  • RAW 264.7 Cells
  • Silicon Dioxide* / chemistry
  • Silicon Dioxide* / pharmacology
  • Tumor Microenvironment* / drug effects

Substances

  • Silicon Dioxide
  • NF-kappa B

Grants and funding

This work is supported by the National Natural Science Foundation of China (82073277 and 82173247), Chongqing Talents: Exceptional Young Talents Project (CQYC2020058650), the Natural Science Foundation of Chongqing (cstc2021ycjh-bgzxm0105), Program for Youth Innovation in Future Medicine, Chongqing Medical University (W0038), the Science and Technology Project Affiliated to the Education Department of Chongqing (KJQN202100404), Science and Technology Project of Chongqing Yuzhong District (20200110) and Project of Chongqing Natural Science Foundation Innovation and Development Fund (Municipal Education Commission) (2022NSCQ-LZX0020). Z.Z. and C.C. are granted by Chongqing Bayu Young. Scholar program. Research and Innovation Projects for Graduate Students of Chongqing (CYS22376).