CNS tumors remain among the deadliest forms of cancer, resisting conventional and new treatment approaches, with mortality rates staying practically unchanged over the past 30 years. One of the primary hurdles for treating these cancers is delivering drugs to the brain tumor site in therapeutic concentration, evading the blood-brain (tumor) barrier (BBB/BBTB). Supramolecular nanomedicines (NMs) are increasingly demonstrating noteworthy prospects for addressing these challenges utilizing their unique characteristics, such as improving the bioavailability of the payloadsviacontrolled pharmacokinetics and pharmacodynamics, BBB/BBTB crossing functions, superior distribution in the brain tumor site, and tumor-specific drug activation profiles. Here, we review NM-based brain tumor targeting approaches to demonstrate their applicability and translation potential from different perspectives. To this end, we provide a general overview of brain tumor and their treatments, the incidence of the BBB and BBTB, and their role on NM targeting, as well as the potential of NMs for promoting superior therapeutic effects. Additionally, we discuss critical issues of NMs and their clinical trials, aiming to bolster the potential clinical applications of NMs in treating these life-threatening diseases.
Keywords: Blood-brain (tumor) barrier; Chemotherapy; Clinical translation; Glioblastoma; Immunotherapy; Nanocarriers; Transcytosis.
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