U87型
体内
下调和上调
药物输送
车站3
癌症研究
免疫系统
医学
血脑屏障
胶质母细胞瘤
体外
离体
免疫学
化学
生物
中枢神经系统
信号转导
细胞生物学
内科学
有机化学
生物技术
基因
生物化学
作者
Jeffrey A. Gregory,Padma Kadiyala,Robert Doherty,Melissa Cadena,Samer Habeel,Erkki Ruoslahti,Pedro R. Löwenstein,María G. Castro,Joerg Lahann
标识
DOI:10.1038/s41467-020-19225-7
摘要
Abstract Glioblastoma (GBM), the most aggressive form of brain cancer, has witnessed very little clinical progress over the last decades, in part, due to the absence of effective drug delivery strategies. Intravenous injection is the least invasive drug delivery route to the brain, but has been severely limited by the blood-brain barrier (BBB). Inspired by the capacity of natural proteins and viral particulates to cross the BBB, we engineered a synthetic protein nanoparticle (SPNP) based on polymerized human serum albumin (HSA) equipped with the cell-penetrating peptide iRGD. SPNPs containing siRNA against Signal Transducer and Activation of Transcription 3 factor (STAT3 i ) result in in vitro and in vivo downregulation of STAT3, a central hub associated with GBM progression. When combined with the standard of care, ionized radiation, STAT3 i SPNPs result in tumor regression and long-term survival in 87.5% of GBM-bearing mice and prime the immune system to develop anti-GBM immunological memory.
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