Optical Stimulation Opens New Possibilities for Glioblastoma Treatment

Abstract Glioblastoma (GBM) represents the most aggressive form of primary brain tumor, characterized by a poor prognosis attributable to its invasive nature and resistance to conventional therapies. A primary challenge in treating GBM is overcoming the blood–brain barrier (BBB) and the blood–brain tumor barrier (BBTB), which significantly impedes drug delivery to the tumor site. Nanoparticles, particularly gold nanoparticles (AuNPs), are emerging as promising tools to facilitate drug delivery across these barriers. AuNPs, with their capability to conjugate therapeutic agents and target molecules, exhibit the potential for localized bypassing of the BBB/BBTB and enhancing drug delivery. This review summarizes the advances in a novel technique coined OptoBBB developed by Li et al, which employs transcranial optical stimulation of AuNPs to reversibly permeabilize the BBB. This approach leverages the photoacoustic effect of plasmonic AuNPs to generate localized pressure waves that modulate endothelial cell junctions, thereby increasing paracellular permeability. OptoBBB has demonstrated its potential to enhance drug delivery to the central nervous system (CNS), specifically GBM. Preclinical models harnessing AuNPs have shown promising results in enhancing drug penetration and improving survival rates. The clinical utility of OptoBBB rests in its ability to target specific brain regions while minimizing damage to surrounding healthy tissue. This review will investigate the current state of OptoBBB as a viable method of facilitating drug delivery to the CNS and describe challenges neurosurgeons may face when looking toward clinical translation.