Size-variable self-feedback nanomotors for glioblastoma therapy via mitochondrial mineralization

Tiantian Chen, Yu Duan, Yingjie Wang, Tiantian Liang, Shiluan Liu, Xue Xia, Chun Mao () and Mimi Wan ()
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Tiantian Chen: Nanjing Normal University
Yu Duan: Nanjing Normal University
Yingjie Wang: Nanjing Normal University
Tiantian Liang: Nanjing Normal University
Shiluan Liu: Nanjing Normal University
Xue Xia: Nanjing Normal University
Chun Mao: Nanjing Normal University
Mimi Wan: Nanjing Normal University

Nature Communications, 2025, vol. 16, issue 1, 1-19

Abstract: Abstract Developing targeted treatment for glioblastoma is crucial but challenging. Herein, we propose a size-variable self-feedback nanomotor system, utilizing the unique high-calcium microenvironment of glioblastoma to prevent its progression through mitochondrial mineralization. It comprises three components: a self-feedback degradable lipid shell (containing nitric oxide-releasing lipid and nitric oxide-responsive degradable lipid), a motion nanomotor core (containing L-arginine derivatives and carboxyl-rich zwitterionic monomers for Ca2+ recruitment), and curcumin (inhibiting Ca2+ efflux). Nitric oxide-releasing lipid can be catalyzed by inducible nitric oxide synthase to release nitric oxide, triggering nitric oxide-responsive degradable lipid degradation. Initially, the larger nanomotors (~ 500 nm) penetrate the blood-brain barrier via chemotaxis towards glioblastoma microenvironment. During chemotaxis, the lipid shell gradually degrades, releasing smaller nanomotor core (~50 nm), which can target mitochondria and recruit Ca2+ to induce mitochondrial mineralization together with curcumin, inhibiting glioblastoma progression. This work may provide a glioblastoma-specific treatment strategy.

Date: 2025
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DOI: 10.1038/s41467-025-64020-x

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