Research Advances on Organelle-Targeted Drug Delivery Systems for the Treatment of Brain Tumors and Central Nervous...

Central nervous system (CNS) inflammation and brain tumor treatment are constrained by the heterogeneity of the blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB), as well as by the sequential barriers to drug delivery across lesions, target cells and subcellular organelles. Simply increasing brain exposure does not ensure that drugs reach their actual sites of action. This review systematically examines the pathological roles and therapeutic rationales of mitochondrial, lysosomal, nuclear, endoplasmic reticulum and Golgi apparatus dysfunction in neuroinflammation and glioblastoma within a two-stage delivery framework encompassing barrier crossing, lesion accumulation, cellular uptake and subcellular organelle localization. It also summarizes key design considerations for liposomes, polymeric nanoparticles, biomimetic membrane-based carriers, exosome-like carriers and focused ultrasound-assisted delivery strategies. Furthermore, translational bottlenecks are discussed, including BBB/BBTB heterogeneity, endosomal/lysosomal escape, organelle off-targeting, long-term safety and the extrapolation of preclinical models. Finally, personalized delivery designs guided by cascade targeting, dynamic visualization-based validation and disease stratification are proposed to support precise treatment of CNS inflammation and brain tumors.