The current standard of care for glioblastoma multiforme, an aggressive brain cancer, is temozolomide (TMZ). While effective in inducing DNA damage and cell cycle arrest, tumor resistance commonly arises. Recent advances in cannabinoid-based therapies, particularly cannabidiol (CBD), have shown promise in synergizing with TMZ to enhance cytotoxicity and modulate the tumor microenvironment. However, even this combination therapy faces limitations due to emerging resistance pathways.
Our technology, SCOPE, is a novel nanoscale (30–100 nm) emulsion formulation created from Spectrum cannabidiol, with a Hydroxy-docosahexaenoic acid (HDHA)-rich fish oil extract, known for its anti-tumor and anti-inflammatory properties, containing 17-HDHA and 14-HDHA. SCOPE is designed to synergize with TMZ in the treatment of glioblastoma multiforme. Experiments showed that SCOPE significantly enhances the therapeutic efficacy of CBD by lowering its IC₅₀ in GBM cell lines and demonstrating synergistic effects with temozolomide (TMZ) at key concentrations. In organoid models, SCOPE treatment led to marked reductions in proliferation and inflammation markers, indicating dual anti-tumor and anti-inflammatory activity. Its nanoemulsion design enables superior brain delivery via intranasal administration compared to oral routes, positioning SCOPE as a non-invasive, targeted therapy. By integrating HDHA lipids into a precision-engineered formulation, SCOPE offers a scalable and clinically translatable platform that addresses resistance mechanisms and improves patient outcomes.
SCOPE treatment significantly reduced Ki67 and IBA1 expression in CT2A brain tumoroids. (A) Immunofluorescent images of stained cryosectioned tumoroids for Ki67 and IBA1 expressions where ki67 is the upper panel and IBA1 is the lower panel. Histogram depicting ki67 (B) and IBA1 (C) expression.