Restoration of p53 mRNA combined with BRD4 silencing by brain targeted nanocapsules achieves effective combinatorial treatment of glioblastoma.

Glioblastoma (GB) is a highly malignant and the most lethal intracranial tumor. p53 mutations in GB patients, occurring in 30-50 % of cases, disrupt tumor-suppressive pathways and promote malignant progression. Advances in mRNA technology enable p53 restoration for GB therapy, but inefficient brain delivery systems limit its use. Additionally, p53 alone may not fully suppress tumors due to compensatory signaling, necessitating the targeting of multiple pathways for better effect. BRD4 is frequen...