The Dynamic Interactions between Nanoparticles and Macrophages Impact Their Fate in Brain Tumors. Issue 49 (12th October 2021)

• Record Type: Journal Article
• Authors: Feng, Qishuai; Xu, Xianyun; Wei, Chen; Li, Yingze; Wang, Min; Lv, Cheng; Wu, Jiaojiao; Dai, Yalei; Han, Yu; Lesniak, Maciej S.; Fan, Haiming; Zhang, Ling; Cheng, Yu
• Is Part Of: Small. Volume 17:Issue 49(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-10-12
• Subjects: brain tumor -- cerebrospinal fluid -- ferumoxytol -- iron oxide nanoparticles -- microglia and macrophages; Nanotechnology -- Periodicals; Nanoparticles -- Periodicals; Microtechnology -- Periodicals; 620.5
• DOI: 10.1002/smll.202103600
• Languages: English
• ISSNs: 1613-6810

Abstract

Abstract: 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. Abstract : The in vivo dynamic fate of ferumoxytol in the tumor brain is revealed over a long period of time, which mainly includes immune recognition of microglia and macrophages, extracellular vesicle‐mediated excretion, the time‐dependent clearance along with cerebrospinal fluid circulation. Herein, it provides a valuable reference for translational applications of iron oxide nanoparticles in brain tumors post intratumoral injection.