胶质瘤
药物输送
药理学
癌症研究
医学
血脑屏障
雷公藤醇
细胞凋亡
化学
中枢神经系统
内科学
生物化学
有机化学
作者
Siqi Zhu,Feifei Sun,Pengfei Zhao,Gang Li,Sun X,Ling‐Hui Zeng,Yongzhuo Huang
标识
DOI:10.1016/j.ijpharm.2022.121709
摘要
The treatment of glioblastoma remains a huge challenge due to the lack of an efficient way to deliver drugs across the blood-brain barrier (BBB), and the pharmacotherapy options are very limited. In this work, a biomimetic BBB-penetrating albumin nanosystem modified by a brain-targeting peptide was designed for co-delivering a TGF-β receptor I (TGFβRI) inhibitor (LY2157299) and an mTOR inhibitor (celastrol). The albumin nanosystem can target nAChRs overexpressed both on the BBB and glioma cells, thereby promoting drug delivery into the glioma. The biomimetic nanoparticles could repolarize tumor-associated macrophages (TAMs) from M2 to M1 phenotype by suppressing the STAT6 pathway, thereby reducing TGF-β1 secretion and inducing cell apoptosis. In addition, the treatment also blocked TGF-β/SMAD2 signaling pathway. The glioma-targeting ability and therapeutic efficacy were confirmed in an orthotopic glioma mouse model. The biomimetic nanoparticles significantly prolonged the survival rate, showing a decrease in the proportion of M2-like TAMs and the levels of TGF-β1 and lactic acid in the glioma tissues. This delivery and treatment strategy provides a new approach for the treatment of gliomas.
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