Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/162296
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. https://dx.doi.org/10.1021/acsnano.1c09480
Project: NRF-NRFI2018-03 
CRP26-2021-0058
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.
URI: https://hdl.handle.net/10356/162296
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

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