Zhang Xiaopei, Artz Nichole, Steindler Dennis A, Hingtgen Shawn, Satterlee Andrew Benson
Eshelman School of Pharmacy, Division of Pharmacoengineering and Molecular Pharmaceutics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Department of Pediatric Hematology/Oncology, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
Biochim Biophys Acta Rev Cancer. 2025 Jul;1880(3):189300. doi: 10.1016/j.bbcan.2025.189300. Epub 2025 Mar 15.
The blood-brain barrier (BBB) presents a major challenge for the effective delivery of therapeutic agents to the brain tumor cells from the peripheral blood circulation, making the treatment of central nervous system (CNS)-related cancers more difficult and resistant to both standard treatments and emerging therapies. Exosomes, which serve as messengers for intercellular communication throughout the body, can naturally or be modified to penetrate the BBB. Recently, exosomes have been increasingly explored as an invasive or non-invasive approach for delivering therapeutic agents to the CNS. With their low immunogenicity, ease of modification, excellent cargo protection, and inherent ability to cross the BBB, exosomes hold great promise for revolutionizing targeted therapy for CNS-related diseases, including brain cancer. In this review, we highlight recent discoveries and insights into the mechanisms exosomes use to penetrate the BBB, the methods they employ to payload diverse therapeutics, and their roles in transporting therapeutic compounds for brain cancer and other neurological disorders.
血脑屏障(BBB)对从外周血液循环向脑肿瘤细胞有效递送治疗药物构成了重大挑战,使得中枢神经系统(CNS)相关癌症的治疗更加困难,并且对标准治疗和新兴疗法均具有抗性。外泌体作为全身细胞间通讯的信使,可以自然穿透血脑屏障,也可以经过修饰后穿透血脑屏障。最近,外泌体作为一种向中枢神经系统递送治疗药物的侵入性或非侵入性方法,受到了越来越多的探索。由于其低免疫原性、易于修饰、出色的货物保护能力以及天然的穿越血脑屏障的能力,外泌体在革新包括脑癌在内的中枢神经系统相关疾病的靶向治疗方面具有巨大潜力。在这篇综述中,我们重点介绍了外泌体穿透血脑屏障的机制、携带多种治疗药物的方法以及它们在为脑癌和其他神经疾病转运治疗化合物中的作用等方面的最新发现和见解。