A switch-on chemo-photothermal nanotherapy impairs glioblastoma

Judiciously combined modality approaches have proved highly effective for treating most forms of cancer, including glioblastoma. This study introduces a hybrid nanoparticle-based treatment designed to induce a synergistic effect. It employs repurposed celecoxib-loaded hybrid nanoparticles (HNPs) that are thermally activated by near-infrared laser irradiation to damage glioblastoma cells. The HNPs are constructed by covalently binding organic (ultra-small nanostructured lipid carriers, usNLCs) and inorganic nanoparticles (gold nanorods, AuNRs, with photothermal therapy capability), using c(RGDfK) that serves the dual purpose of a biolinker and a tumor-targeting peptide. The HNPs are further functionalized with transferrin (Tf) as a blood-brain barrier ligand denoted as HNPs^Tf. Our comprehensive <i>in vitro</i> and <i>in vivo</i> studies have unveiled the remarkable capability of HNPs^Tf to safely and specifically increase blood-brain barrier permeability through transferrin receptor interactions, facilitating precise nanoparticle accumulation in the tumor region within orthotopic tumor-bearing mice. Furthermore, the orchestrated combination of chemo- and photothermal therapy has exhibited a substantial therapeutic impact on glioblastoma, showcasing a noteworthy 78% inhibition in tumor volume growth and an impressive 98% delay in tumor growth. Notably, this treatment approach has resulted in prolonged survival rates among tumor-bearing mice, accompanied by a favorable side effect profile. Overall, our findings unequivocally demonstrate that celecoxib-loaded HNPs^Tf offer a game-changing, chemo-photothermal combination, unleashing a synergistic effect that significantly enhances both brain drug delivery and the efficacy of anti-glioblastoma treatments.