ABSTRACT Glioblastoma—the most aggressive and lethal primary brain malignancy—is pathologically associated with aberrant enantiomeric ratios of amino acids. This chiral imbalance catalyzes the exploration of leveraging chirality in nano‐engineering glioblastoma therapy; yet, it remains unproven due to challenges in precise regulation and in‐depth understanding of chirality‐neuro system interactions. Herein, we propose a helix‐and‐modification‐of‐surface‐atoms strategy, producing biocompatible chiral gold nanorods with intrinsic nanohelical morphology. The strong and tunable chiroptical activity selectively upregulates key pro‐apoptotic genes while downregulating certain pro‐proliferative ones, demonstrating nanoscaled chirality‐dependent glioblastoma suppression. Notably, in vivo evolutions show that right‐handed helices exhibit potent inhibition of PI3K‐Akt and MAPK signaling cascades, resulting in an 81.2% reduction in intracranial tumor area compared to their left‐handed counterparts. These findings reveal that chirality‐engineered gold nanorods enantioselectively modulate gene expression and inhibit critical signaling pathways activated in cancer cells, providing a novel therapeutic avenue for glioblastoma and beyond.
Tong et al. (Wed,) studied this question.