Atorvastatin-Driven Methuosis in Glioblastoma: A Biomimetic Nanodrug for Targeted Tumor Therapy.

Glioblastoma (GBM) is a highly malignant brain tumor. The immunosuppressive microenvironment and resistance to chemotherapy-induced apoptosis pose significant challenges for treatment. In this study, we found that atorvastatin calcium (AC) can effectively induce methuosis in GBM cells, suggesting its potential as a therapeutic candidate for GBM treatment. To address the challenge of crossing the blood-brain barrier (BBB) and enhance drug delivery efficiency, we synthesized AC nanoparticles stabilized through dopamine polymerization, achieving high drug-loading efficiency. Moreover, the nanoparticles were coated with PD-1-engineered BV2 cell membranes and further modified with Angiopep-2 peptides to facilitate BBB crossing and effective accumulation at the tumor site. In vitro experiments confirmed the cytotoxicity and induction of methuosis in GBM cells by AP@CM-Ang, accompanied by the release of immune-stimulatory factors. In vivo experiments demonstrated that the nanodrug significantly enhanced tumor targeting, effectively inhibited tumor growth, and increased immune cell activation, validating its potential as a promising and safe strategy for GBM treatment.