Targeted Microglial\nMembrane-Coated MicroRNA Nanosponge\nMediates Inhibition of Glioblastoma

Glioblastoma (GBM) is the most prevalent primary brain\ntumor. Recent\nresearch emphasizes the crucial role of microRNAs (miRs) in GBM pathogenesis,\nand targeting miRs offers an effective approach for precise GBM therapy.\nHowever, inhibiting a single miR may not be sufficient due to the\ncompensatory mechanisms of GBM. Herein, we developed a miR-nanosponge\ncapable of specifically capturing multiple miRs involved in tumor\ngrowth, migration, invasion, angiogenesis, and the creation of an\nimmunosuppressive microenvironment, thereby offering a comprehensive\ntreatment for GBM. Coated with BV2 cell membrane (BM) for enhanced\nblood–brain barrier (BBB) crossing and GBM targeting, the BM@miR-nanosponge\ntargets miR-9, miR-21, miR-215, and miR-221, significantly inhibiting\nGBM progression and modulating the immune system for a thorough GBM\neradication. The BM@miR-nanosponge notably extended the median survival\ntime of GBM-bearing mice and outperformed the standard treatment drug\ntemozolomide (TMZ). This study introduces a comprehensive miR-based\nstrategy for GBM treatment and highlights the importance of targeting\nmultiple miRs associated with tumor survival for effective therapy.