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Transformable Helical Self-Assembly for Cancerous Golgi Apparatus Disruption
Nano Letters ( IF 10.8 ) Pub Date : 2021-09-27 , DOI: 10.1021/acs.nanolett.1c03112
Rong Sheng Li 1, 2 , Jiahui Liu 1 , Hu Shi 3 , Ping Ping Hu 4 , Yao Wang 1 , Peng Fei Gao 1 , Jian Wang 1 , Moye Jia 5 , Hongwei Li 5 , Yuan Fang Li 6 , Chengde Mao 1, 7 , Na Li 2 , Cheng Zhi Huang 1
Affiliation  

Golgi apparatus is a major subcellular organelle responsible for drug resistance. Golgi apparatus-targeted nanomechanical disruption provides an attractive approach for killing cancer cells by multimodal mechanism and avoiding drug resistance. Inspired by the poisonous twisted fibrils in Alzheimer’s brain tissue and enhanced rigidity of helical structure in nature, we designed transformable peptide C6RVRRF4KY that can self-assemble into nontoxic nanoparticles in aqueous medium but transformed into left-handed helical fibrils (L-HFs) after targeting and furin cleavage in the Golgi apparatus of cancer cells. The L-HFs can mechanically disrupt the Golgi apparatus membrane, resulting in inhibition of cytokine secretion, collapse of the cellular structure, and eventually death of cancer cells. Repeated stimulation of the cancers by the precursors causes no acquired drug resistance, showing that mechanical disruption of subcellular organelle is an excellent strategy for cancer therapy without drug resistance. This nanomechanical disruption concept should also be applicable to multidrug-resistant bacteria and viruses.

中文翻译:

用于癌症高尔基体装置破坏的可变形螺旋自组装

高尔基体是负责耐药性的主要亚细胞器。高尔基体靶向纳米机械破坏为通过多模式机制杀死癌细胞和避免耐药性提供了一种有吸引力的方法。受阿尔茨海默病脑组织中有毒的扭曲原纤维和自然界中螺旋结构刚性增强的启发,我们设计了可转化肽 C 6 RVRRF 4KY 可以在水性介质中自组装成无毒纳米颗粒,但在癌细胞的高尔基体中靶向和弗林蛋白酶裂解后转化为左旋螺旋原纤维 (L-HF)。L-HFs 可以机械破坏高尔基体膜,导致细胞因子分泌抑制、细胞结构崩溃,并最终导致癌细胞死亡。前体对癌症的反复刺激不会导致获得性耐药,这表明亚细胞器的机械破坏是无耐药性癌症治疗的极好策略。这种纳米机械破坏概念也应该适用于多重耐药细菌和病毒。
更新日期:2021-10-13
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