Please use this identifier to cite or link to this item:
Title: Cell-specific metabolic reprogramming of tumors for bioactivatable ferroptosis therapy
Authors: Li, Yanan
Li, Menghuan
Liu, Li
Xue, Chencheng
Fei, Yang
Wang, Xuan
Zhang, Yuchen
Cai, Kaiyong
Zhao, Yanli
Luo, Zhong
Keywords: Science::Chemistry::Biochemistry
Issue Date: 2022
Source: Li, Y., Li, M., Liu, L., Xue, C., Fei, Y., Wang, X., Zhang, Y., Cai, K., Zhao, Y. & Luo, Z. (2022). Cell-specific metabolic reprogramming of tumors for bioactivatable ferroptosis therapy. ACS Nano, 16(3), 3965-3984.
Project: NRF-NRFI2018-03 
Journal: ACS Nano
Abstract: Ferroptosis is a nonapoptotic iron-dependent cell death pathway with a significant clinical potential, but its translation is impeded by lack of tumor-specific ferroptosis regulators and aberrant tumor iron metabolism. Herein, we report a combinational strategy based on clinically tested constituents to selectively induce ferroptosis in metabolically reprogrammed tumor cells through cooperative GPX4-inhibition and ferritinophagy-enabled Fe2+ reinforcement. Azido groups were first introduced on tumor cells using biocompatible long-circulating self-assemblies based on polyethylene glycol-disulfide-N-azidoacetyl-d-mannosamine via metabolic glycoengineering. The azido-expressing tumor cells could specifically react with dibenzocyclooctyne-modified disulfide-bridged nanoassemblies via bioorthogonal click reactions, where the nanoassemblies were loaded with ferroptosis inducer RSL3 and ferritinophagy initiator dihydroartemisinin (DHA) and could release them in a bioresponsive manner. DHA-initiated ferritinophagy could degrade intracellular ferritin to liberate stored iron species and cooperate with the RSL3-mediated GPX4-inhibition for enhanced ferroptosis therapy. This tumor-specific ferroptosis induction strategy provides a generally applicable therapy with enhanced translatability, especially for tumors lacking targetable endogenous receptors.
ISSN: 1936-0851
DOI: 10.1021/acsnano.1c09480
Rights: © 2022 American Chemical Society. All rights reserved.
Fulltext Permission: none
Fulltext Availability: No Fulltext
Appears in Collections:SPMS Journal Articles

Citations 50

Updated on Nov 29, 2022

Web of ScienceTM
Citations 50

Updated on Nov 27, 2022

Page view(s)

Updated on Dec 3, 2022

Google ScholarTM




Items in DR-NTU are protected by copyright, with all rights reserved, unless otherwise indicated.