Systemic brain tumor delivery of synthetic protein nanoparticles for glioblastoma therapy.
Systemic brain tumor delivery of synthetic protein nanoparticles for glioblastoma therapy.
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用于胶质母细胞瘤治疗的合成蛋白纳米颗粒的全身性脑肿瘤递送。
DOI：
10.1038/s41467-020-19225-7
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发表时间：
2020-11-10
影响因子：
16.6
通讯作者：
Lahann J
中科院分区：
文献类型：
--
作者：
Gregory JV;Kadiyala P;Doherty R;Cadena M;Habeel S;Ruoslahti E;Lowenstein PR;Castro MG;Lahann J
胶质母细胞瘤（GBM）是脑癌中最具侵袭性的一种，在过去的几十年里，其临床进展甚微，部分原因是缺乏有效的药物递送策略。静脉注射是最小侵入性的药物递送途径，但受到血脑屏障（BBB）的严重限制。受天然蛋白质和病毒颗粒穿过血脑屏障的能力的启发，我们设计了一种基于聚合人血清白蛋白（HSA）的合成蛋白纳米颗粒（SPNP），该蛋白纳米颗粒配备了细胞穿透肽iRGD。含有针对信号转导和转录激活3因子（STAT3i）的siRNA的SPNP导致STAT3（与GBM进展相关的中心枢纽）的体外和体内下调。当与标准治疗、电离辐射、STAT3i SPNP组合时，在87.5%的携带GBM的小鼠中导致肿瘤消退和长期存活，并引发免疫系统发展抗GBM免疫记忆。缺乏有效的药物递送策略已经阻碍了胶质母细胞瘤（GBM）治疗的进展。在这里，作者设计了基于聚合人血清白蛋白的合成蛋白纳米颗粒，配备了细胞穿透肽iRGD，以提供针对STAT3的siRNA，并报告了GBM小鼠模型的存活率提高。
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 (STAT3i) 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, STAT3i 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. The lack of effective drug delivery strategies has impaired the therapeutic progress in the treatment of glioblastoma (GBM). Here, the authors engineer synthetic protein nanoparticle based on polymerized human serum albumin equipped with the cell-penetrating peptide iRGD to deliver siRNA against STAT3 and report improved survival in a mouse model of GBM.
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影响因子：
14
作者：
Gaudin, Alice;Song, Eric;King, Amanda R.;Saucier-Sawyer, Jennifer K.;Bindra, Ranjit;Desmaele, Didier;Couvreur, Patrick;Saltzman, W. Mark
通讯作者：
Saltzman, W. Mark
影响因子：
5
作者：
Desai, Neil;Trieu, Vuong;Soon-Shiong, Patrick
通讯作者：
Soon-Shiong, Patrick
影响因子：
1.1
作者：
Davis ME
通讯作者：
Davis ME
影响因子：
--
作者：
Ganguly D;Fan M;Yang CH;Zbytek B;Finkelstein D;Roussel MF;Pfeffer LM
通讯作者：
Pfeffer LM
DOI：
10.1073/pnas.1114518108
发表时间：
2011-10-18
影响因子：
11.1
作者：
Agemy, Lilach;Friedmann-Morvinski, Dinorah;Ruoslahti, Erkki
通讯作者：
Ruoslahti, Erkki