A Chiral Virus‐Like Nanoplatform That Broadly Mediates Antibiotic Delivery to the Brain for Bacterial Meningitis Therapy

ABSTRACT Blood‐brain barrier (BBB) preserves brain homeostasis yet restricts therapeutics; in bacterial meningitis, antibiotics’ limited penetration impairs delivery to the parenchyma and cerebrospinal fluid, constraining efficacy and motivating strategies to overcome the barrier. To address this, we developed a chiral virus‐mimicking mesoporous silica nanostructure (CVSN) functionalized with L‐alanine for antibiotic delivery. It offers several distinct advantages: (1) nanoscale dimensions facilitating BBB transport; (2) virus‐like morphology enhancing vascular accumulation and penetration, providing a foundation for passive targeting; (3) chiral surface modification conferring active recognition capacity for more efficient biological targeting; and (4) a mesoporous architecture that ensures high drug‐loading efficiency and controlled release of drugs. Experimentally, it achieves efficient BBB penetration into the brain parenchyma and shows targeted delivery into microglia and astrocytes. Simulating the loading of cargoes by viruses, it ultimately improves the bioavailability and brain parenchyma and cerebrospinal fluid contents of various antibiotics with distinct physicochemical properties, antibacterial spectrum, and BBB penetration capacity, including cefoperazone, norfloxacin, levofloxacin and imipenem. It helps to treat meningitis induced by both Gram‐negative bacteria (e.g., Escherichia coli ) and Gram‐positive bacteria (e.g., Staphylococcus aureus ) and provides a promising avenue to overcome the limitations imposed by the BBB for CNS infections antibiotic therapy in clinic.