当前位置: X-MOL 学术Mol. Cancer Ther. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
A Novel Theranostic Strategy for MMP-14-Expressing Glioblastomas Impacts Survival
Molecular Cancer Therapeutics ( IF 5.7 ) Pub Date : 2017-09-01 00:00:00 , DOI: 10.1158/1535-7163.mct-17-0022
Suchismita Mohanty , Zixin Chen , Kai Li , Goreti Ribeiro Morais , Jessica Klockow , Ketan Yerneni , Laura Pisani , Frederick T. Chin , Siddharta Mitra , Samuel Cheshier , Edwin Chang , Sanjiv Sam Gambhir , Jianghong Rao , Paul M. Loadman , Robert A. Falconer , Heike E. Daldrup-Link

Glioblastoma (GBM) has a dismal prognosis. Evidence from preclinical tumor models and human trials indicates the role of GBM-initiating cells (GIC) in GBM drug resistance. Here, we propose a new treatment option with tumor enzyme-activatable, combined therapeutic and diagnostic (theranostic) nanoparticles, which caused specific toxicity against GBM tumor cells and GICs. The theranostic cross-linked iron oxide nanoparticles (CLIO) were conjugated to a highly potent vascular disrupting agent (ICT) and secured with a matrix-metalloproteinase (MMP-14) cleavable peptide. Treatment with CLIO-ICT disrupted tumor vasculature of MMP-14 –expressing GBM, induced GIC apoptosis, and significantly impaired tumor growth. In addition, the iron core of CLIO-ICT enabled in vivo drug tracking with MR imaging. Treatment with CLIO-ICT plus temozolomide achieved tumor remission and significantly increased survival of human GBM-bearing mice by more than 2-fold compared with treatment with temozolomide alone. Thus, we present a novel therapeutic strategy with significant impact on survival and great potential for clinical translation. Mol Cancer Ther; 16(9); 1909–21. ©2017 AACR .

中文翻译:

一种表达MMP-14的胶质母细胞瘤的新型治疗方法影响生存

胶质母细胞瘤(GBM)的预后不良。临床前肿瘤模型和人体试验的证据表明,GBM起始细胞(GIC)在GBM耐药性中的作用。在这里,我们提出了一种新的治疗方案,可利用可激活肿瘤酶的,治疗性和诊断性(热疗性)纳米粒子相结合,从而对GBM肿瘤细胞和GIC产生特异性毒性。治疗性交联的氧化铁纳米颗粒(CLIO)与高效血管破坏剂(ICT)偶联,并用基质金属蛋白酶(MMP-14)可裂解肽固定。CLIO-ICT的治疗破坏了表达MMP-14的MMP-14的肿瘤血管,诱导了GIC凋亡,并显着损害了肿瘤的生长。此外,CLIO-ICT的铁芯可通过MR成像进行体内药物跟踪。与单独使用替莫唑胺治疗相比,用CLIO-ICT加替莫唑胺治疗可实现肿瘤缓解,并使人GBM小鼠的存活率显着提高2倍以上。因此,我们提出了一种新颖的治疗策略,对生存率具有重大影响,并且具有巨大的临床翻译潜力。分子癌疗法;16(9); 1909–21。©2017 AACR。
更新日期:2017-09-05
down
wechat
bug