替莫唑胺
荧光
RNA干扰
粒子(生态学)
类病毒颗粒
病毒学
纳米技术
癌症研究
胶质母细胞瘤
材料科学
化学
生物
核糖核酸
物理
生物化学
基因
生态学
量子力学
重组DNA
作者
Hao‐Han Pang,Chiung-Yin Huang,Ya-Wen Chou,Chia-Jung Lin,Zi-Lin Zhou,Yow‐Ling Shiue,Kuo‐Chen Wei,Hung‐Wei Yang
出处
期刊:Nanoscale
[The Royal Society of Chemistry]
日期:2019-01-01
卷期号:11 (17): 8102-8109
被引量:32
摘要
The proof-of-concept strategy in this study based on biodegradable and biocompatible self-assembling fluorescent virus-like particle/RNAi nanocomplexes (VLP/RNAi) produced in Escherichia coli (E. coli) followed by surface modification with a cell-penetrating peptide (CPP) and an apolipoprotein E peptide (ApoEP) (dP@VLP/RNAi), which can cross the blood-brain barrier (BBB) to inhibit the DNA repair mechanism and act synergistically with temozolomide (TMZ) for promoting clinical chemotherapy has achieved good therapeutic effects towards malignant brain tumors. The synergistic value of this study's design was verified in intracranial mouse models of glioblastomas (GBMs). Intravenous administration of this formulation enhanced the curative efficacy of TMZ by downregulating the hepatocyte growth factor receptor (c-MET) gene in GBM U87 cells. Furthermore, upon gene-chemotherapy, the methylated DNA in GBM U87 cells was significantly enhanced by inhibiting the DNA repair mechanism, leading to significant brain tumor suppression. The results of this study could be critical for the design of RNAi-based genetic therapeutics for promoting chemotherapy against brain tumors.
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