The Dynamic Interactions between Nanoparticles and Macrophages Impact Their Fate in Brain Tumors

Qishuai Feng, Xianyun Xu, Chen Wei, Yingze Li, Min Wang, Cheng Lv, Jiaojiao Wu, Yalei Dai, Yu Han, Maciej S. Lesniak, Haiming Fan, Ling Zhang*, Yu Cheng*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Functional nanomaterials such as iron oxide nanoparticles have been extensively explored for the diagnosis and treatment of central nervous system diseases. However, an insufficient understanding of the comprehensive nanomaterial-biological interactions in the brain hinders the nanomaterials from meeting the medical requirements for translational research. Here, FDA-approved ferumoxytol, an iron oxide nanoparticle, is chosen as the model nanomaterial for a systematic study of the dynamic interactions between ferumoxytol and immune cells, including microglia and macrophages, in the brain tumors. Strikingly, up to 90% of intratumorally injected ferumoxytol nanoparticles are recognized and phagocytized by tumor-associated microglia and macrophages. The dynamic trafficking progress of ferumoxytol in microglia and macrophages, including scavenger receptor-mediated endocytosis, lysosomal internalization, and extracellular vesicle-dominated excretion, is further studied. Importantly, the results demonstrate that extracellular vesicle-encapsulated nanoparticles could be gradually eliminated from the brain along with cerebrospinal fluid circulation over 21 days. Moreover, ferumoxytol exhibits no obvious long-term neurological toxicity after its injection. The study suggests that the dynamic biointeractions of nanoparticles with immune cells in the brain exert a key rate-limiting impact on the efficiency of targeting tumor cells and their in vivo fate and thus provide a deeper understanding of the nanomaterials in the brain for clinical applications.

Original languageEnglish (US)
Article number2103600
Issue number49
StatePublished - Dec 9 2021


  • brain tumor
  • cerebrospinal fluid
  • ferumoxytol
  • iron oxide nanoparticles
  • microglia and macrophages

ASJC Scopus subject areas

  • Engineering (miscellaneous)
  • Chemistry(all)
  • Materials Science(all)
  • Biotechnology
  • Biomaterials


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