{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T10:08:55Z","timestamp":1789034935212,"version":"build-2803163510"},"reference-count":156,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CAMS Innovation Fund for Medical Science","award":["2021-I2M-1-026"],"award-info":[{"award-number":["2021-I2M-1-026"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Central nervous system (CNS) inflammation and brain tumor treatment are constrained by the heterogeneity of the blood\u2013brain barrier (BBB) and blood\u2013brain 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.<\/jats:p>","DOI":"10.3390\/pharmaceutics18091140","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T09:13:03Z","timestamp":1789031583000},"page":"1140","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Research\u00a0Advances on Organelle-Targeted Drug Delivery Systems for the Treatment of Brain Tumors and Central Nervous System Inflammation"],"prefix":"10.3390","volume":"18","author":[{"given":"Manru","family":"Zhang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, 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Chengchuang Pharmaceutical Research and Development Co., Ltd., Beijing 102300, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolong","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China"},{"name":"Beijing Key Laboratory of Key Technologies for Natural Drug Delivery and Novel Formulations, Department of Pharmaceutics, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingxian","family":"Sun","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 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College, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liqing","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China"},{"name":"Beijing Key Laboratory of Key Technologies for Natural Drug Delivery and Novel Formulations, Department of Pharmaceutics, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Huang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China"},{"name":"Beijing Key Laboratory of Key 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