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

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. Glioblastoma therapy is challenging, and new approaches are needed. Here, the authors report on a mitochondrial targeting nanomotor with self-feedback mechanisms to trigger the mineralisation of mitochondria which together with curcumin, inhibits glioblastoma progression.