nl1c03112_si_001.pdf (6.01 MB)
Download fileTransformable Helical Self-Assembly for Cancerous Golgi Apparatus Disruption
journal contribution
posted on 27.09.2021, 15:06 authored by Rong Sheng Li, Jiahui Liu, Hu Shi, Ping Ping Hu, Yao Wang, Peng Fei Gao, Jian Wang, Moye Jia, Hongwei Li, Yuan Fang Li, Chengde Mao, Na Li, Cheng Zhi HuangGolgi
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.
History
Usage metrics
Read the peer-reviewed publication
Keywords
poisonous twisted fibrilshanded helical fibrilsnanomechanical disruption concept6 </ sub4 </ subavoiding drug resistanceacquired drug resistancekilling cancer cellsgolgi apparatus membranetransformable helical selfdrug resistancegolgi apparatuscancer cellshelical structuremechanical disruptionsubcellular organelleresistant bacteriarepeated stimulationprecursors causesnontoxic nanoparticlesmultimodal mechanismmechanically disruptfurin cleavageexcellent strategyeventually deathenhanced rigiditycytokine secretioncellular structurebrain tissueattractive approachaqueous mediumalzheimer ’