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

  • ACS Nano. 2026 Apr 14;20(14):10889-10904. doi: 10.1021/acsnano.5c15615.
Xinyan Hao  1  2 ,  Yucheng Tang  1  2 ,  Wenjie Xu  1  2 ,  Ming Wang  3 ,  Jiayi Liu  4 ,  Haitao Yang  5 ,  Pengcheng Sun  1  2 ,  Dehua Liao  6 ,  Xiongbin Hu  1  2 ,  Tiantian Tang  1  2 ,  Hai Huang  1  2 ,  Xinying Liu  1  2 ,  Daxiong Xiang  1  2 ,  Junyong Wu  1  2  7
Affiliations
  • 1. Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha 410011, China.
  • 2. Institute of Clinical Pharmacy, Central South University, Changsha 410011, China.
  • 3. Department of Neurosurgery, The Second Xiangya Hospital, Central South University, Changsha 410011, China.
  • 4. Department of Oncology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.
  • 5. Department of Radiology, The Second Xiangya Hospital, Central South University, Changsha 410011, China.
  • 6. Department of Pharmacy, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410031, China.
  • 7. Hunan Key Laboratory of Tumor Models and Individualized Medicine, The Second Xiangya Hospital, Changsha 410011, China.
PMID: 41933442 DOI: 10.1021/acsnano.5c15615
Abstract

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.

Keywords
BBB penetration; atorvastatin; glioblastoma; methuosis; nanodrug.
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