Dey Mahua, Yu Dou, Kanojia Deepak, Li Gina, Sukhanova Madina, Spencer Drew A, Pituch Katatzyna C, Zhang Lingjiao, Han Yu, Ahmed Atique U, Aboody Karen S, Lesniak Maciej S, Balyasnikova Irina V
The Brain Tumor Center, The University of Chicago, Chicago, IL 60637, USA.
The Brain Tumor Center, The University of Chicago, Chicago, IL 60637, USA; Department of Neurological Surgery, The Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Stem Cell Reports. 2016 Sep 13;7(3):471-482. doi: 10.1016/j.stemcr.2016.07.024. Epub 2016 Sep 1.
The challenges to effective drug delivery to brain tumors are twofold: (1) there is a lack of non-invasive methods of local delivery and (2) the blood-brain barrier limits systemic delivery. Intranasal delivery of therapeutics to the brain overcomes both challenges. In mouse model of malignant glioma, we observed that a small fraction of intranasally delivered neural stem cells (NSCs) can migrate to the brain tumor site. Here, we demonstrate that hypoxic preconditioning or overexpression of CXCR4 significantly enhances the tumor-targeting ability of NSCs, but without altering their phenotype only in genetically modified NSCs. Modified NSCs deliver oncolytic virus to glioma more efficiently and extend survival of experimental animals in the context of radiotherapy. Our findings indicate that intranasal delivery of stem cell-based therapeutics could be optimized for future clinical applications, and allow for safe and repeated administration of biological therapies to brain tumors and other CNS disorders.
（1）缺乏局部递送的非侵入性方法，（2）血脑屏障限制全身递送。经鼻向脑内递送治疗药物克服了这两个挑战。在恶性胶质瘤小鼠模型中，我们观察到经鼻递送的一小部分神经干细胞（NSC）可迁移至脑肿瘤部位。在此，我们证明缺氧预处理或CXCR4过表达可显著增强NSC的肿瘤靶向能力，但仅在基因改造的NSC中不会改变其表型。改造后的NSC能更有效地将溶瘤病毒递送至胶质瘤，并在放疗情况下延长实验动物的生存期。我们的研究结果表明，基于干细胞的治疗药物经鼻递送可针对未来临床应用进行优化，并允许对脑肿瘤和其他中枢神经系统疾病安全且重复地给予生物治疗。
