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Microbial Lipopeptide Supramolecular Self-Assemblies as a Methuosis-Like Cell Death Inducer with In Vivo Antitumor Activity.

Published:11 November 2021 DOI: 10.1002/smll.202104034 PMID: 34761865
Jiao Yang Lu, Wei Tao Huang, Kexuan Zhou, Xiaoli Zhao, Shuqing Yang, Liqiu Xia, Xuezhi Ding

Abstract

Discovering new drugs and improving action mechanisms is a promising strategy to overcome chemotherapy ineffectiveness caused by cancer cell apoptosis resistance. Natural products (like cyclic lipopeptides, CLPs) are potential sources of nonapoptotic cell death inducers and can form diverse supramolecular structures, closely relating to their bioactivities. Herein, it is found for the first time that fatty chain is the key to maintain self-assembled form and antitumor activity of microbial-derived amphiphilic CLP bacillomycin Lb (B-Lb). Compared with B-Lb analogues assemblies without antitumor activity, B-Lb supramolecular self-assemblies (including nanomicelles, nanofibers, giant micrometer rods) can be generated in a multilevel and cross-scale manner and served as a methuosis-like cell death inducer triggered by cytoplasmic vacuolation through macropinocytosis in MDA-MB-231-Luc and MCF-7 cells and in vivo tumor-bearing mice. This study will promote constructing of customized CLP micro-/nanostructures with multipurposes and functions, and boost designing of new antitumor drugs as nonapoptotic cell death modulators based on structure–activity relationship.

Substances (16)

Materials
Procduct Name CAS Molecular Formula Supplier Price
beta-Cyclodextrin methyl ethers 128446-36-6 C54H94O35 430 suppliers $5.00-$14610.00
beta-Cyclodextrin methyl ethers 128446-36-6 C54H94O35 430 suppliers $5.00-$14610.00
beta-Cyclodextrin methyl ethers 128446-36-6 C54H94O35 430 suppliers $5.00-$14610.00
beta-Cyclodextrin methyl ethers 128446-36-6 C54H94O35 430 suppliers $5.00-$14610.00
LY 294002 Hydrochloride 154447-36-6 C19H17NO3 405 suppliers $12.00-$3350.00
LY 294002 Hydrochloride 154447-36-6 C19H17NO3 405 suppliers $12.00-$3350.00
LY 294002 Hydrochloride 154447-36-6 C19H17NO3 405 suppliers $12.00-$3350.00
LY 294002 Hydrochloride 154447-36-6 C19H17NO3 405 suppliers $12.00-$3350.00
Dynasore 304448-55-3 C18H14N2O4 185 suppliers $12.00-$2755.00
Dynasore 304448-55-3 C18H14N2O4 185 suppliers $12.00-$2755.00

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