The blood–brain barrier (BBB) protects the brain; however, it also severely limits drug delivery during glioma therapy. Notably, promising nanotechnology solutions provide biocompatible platforms with improved targeting, enhanced stability, and controlled release. This review outlines the physiological features of the BBB and summarizes the recent advances in nanotechnology-enabled strategies for glioma theranostics. In this review, the following three major approaches are highlighted: (i) crossing the BBB via transcellular transport, including carrier-mediated, receptor-mediated, and adsorption-mediated transcytosis; (ii) enhancing the BBB permeability with physical or chemical modulation, including focused ultrasound, hypertonic agents, electroporation, and magnetic stimulation; and (iii) bypassing the BBB by administering drugs via intrathecal, convection-enhanced, and intranasal routes as well as laser interstitial thermotherapy. Despite substantial advancements, challenges persist, including an incomplete understanding of penetration mechanisms, safety concerns, and the lack of reliable translational models. Thus, integrating nanotechnology with innovative delivery strategies provides promising strategies for more effective and precise glioma theranostics. • Systematically summarizes nanotechnology-enabled strategies that improve drug delivery across the blood–brain barrier for glioma theranostics. • Establishes a unified framework integrating BBB-crossing, BBB-modulation, and BBB-bypass approaches to guide rational design of CNS-targeted nanomedicines. • Highlights advanced transcellular and physicochemical mechanisms—including receptor-mediated transcytosis and focused ultrasound—that enhance therapeutic penetration. • Identifies key translational barriers (mechanistic uncertainty, safety, model limitations) and outlines directions for developing clinically viable nanodrug delivery systems.
YANG et al. (Wed,) studied this question.