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Nano Research 2023, 16(4): 5265-5278 https://doi.org/10.1007/s12274-022-5186-5
Research Article | Issue | Published: 07 December 2022

Design of manganese ion coated Prussian blue nanocarrier for the therapy of refractory diffuse large B-cell lymphoma based on a comprehensive analysis of ferroptosis regulators from clinical cases

Show Author's Information Yulu Yang1,  Rui Chen2,  Ke Li1,  Pengfei Gao1,  Yi Gong3( ),  Weihu Yang1( ),  Kaiyong Cai1( )
Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University, Chongqing 400044, China
Department of Pathology, Chongqing University Cancer Hospital, Chongqing 400030, China
Department of Phase I Clinical Trial Ward, Chongqing University Cancer Hospital, Chongqing 400030, China
Keywords:
tumor therapy, ferroptosis, Prussian blue nanoparticles, diffuse large B-cell lymphoma (DLBCL), manganese ion
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Yang Y, Chen R, Li K, et al. Design of manganese ion coated Prussian blue nanocarrier for the therapy of refractory diffuse large B-cell lymphoma based on a comprehensive analysis of ferroptosis regulators from clinical cases. Nano Research, 2023, 16(4): 5265-5278. https://doi.org/10.1007/s12274-022-5186-5
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Abstract Full text Electronic supplementary material About this article

Diffuse large B-cell lymphoma (DLBCL) is a prevalent human malignancy, and understanding its biology will help identify problems in refractory patients and customize alternative therapies for them. We found that DLBCL can be stratified into two independent subtypes with different clinical characteristics and outcomes by consensus clustering of expression of ferroptosis regulatory genes, which proves that ferroptosis is effective in treating refractory cases. In this work, we constructed a novel ferroptosis nanocarrier (PBPMn@PEG) by coating Prussian blue nanoparticles with manganese ions and encapsulating them with poly(ethyleneglycol). The low efficiency of the Fenton reaction of Prussian blue nanoparticles can be improved greatly by manganese coating, and can effectively generate hydroxyl radicals, and induce ferroptosis of lymphoma cells (SU-DHL-10 cells) by down-regulating ferroptosis suppressor genes and up-regulating ferroptosis driver genes. It also induces effective cell apoptosis, which is synergistic with ferroptosis for DLBCL therapy. In vivo experiments also prove that PBPMn@PEG achieved a better anti-tumor effect by up-regulating COX2, HO-1/hemeoxygenase-1 (HMOX1), and NADPH oxidase-4 (NOX4), and down-regulating FSP1 and GPX4, with lower biotoxicity. As a novel and potential DLBCL drug carrier, our discovery served as a foundation for the treatment of the refractory DLBCL by inducing ferroptosis for DLBCL treatment in addition to the therapeutic effect of drugs.


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About this article

Design of manganese ion coated Prussian blue nanocarrier for the therapy of refractory diffuse large B-cell lymphoma based on a comprehensive analysis of ferroptosis regulators from clinical cases

Show Author's information Yulu Yang1, Rui Chen2, Ke Li1, Pengfei Gao1, Yi Gong3( ), Weihu Yang1( ), Kaiyong Cai1( )
Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University, Chongqing 400044, China
Department of Pathology, Chongqing University Cancer Hospital, Chongqing 400030, China
Department of Phase I Clinical Trial Ward, Chongqing University Cancer Hospital, Chongqing 400030, China

Abstract

Diffuse large B-cell lymphoma (DLBCL) is a prevalent human malignancy, and understanding its biology will help identify problems in refractory patients and customize alternative therapies for them. We found that DLBCL can be stratified into two independent subtypes with different clinical characteristics and outcomes by consensus clustering of expression of ferroptosis regulatory genes, which proves that ferroptosis is effective in treating refractory cases. In this work, we constructed a novel ferroptosis nanocarrier (PBPMn@PEG) by coating Prussian blue nanoparticles with manganese ions and encapsulating them with poly(ethyleneglycol). The low efficiency of the Fenton reaction of Prussian blue nanoparticles can be improved greatly by manganese coating, and can effectively generate hydroxyl radicals, and induce ferroptosis of lymphoma cells (SU-DHL-10 cells) by down-regulating ferroptosis suppressor genes and up-regulating ferroptosis driver genes. It also induces effective cell apoptosis, which is synergistic with ferroptosis for DLBCL therapy. In vivo experiments also prove that PBPMn@PEG achieved a better anti-tumor effect by up-regulating COX2, HO-1/hemeoxygenase-1 (HMOX1), and NADPH oxidase-4 (NOX4), and down-regulating FSP1 and GPX4, with lower biotoxicity. As a novel and potential DLBCL drug carrier, our discovery served as a foundation for the treatment of the refractory DLBCL by inducing ferroptosis for DLBCL treatment in addition to the therapeutic effect of drugs.

Keywords: tumor therapy, ferroptosis, Prussian blue nanoparticles, diffuse large B-cell lymphoma (DLBCL), manganese ion

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Publication history
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Acknowledgements

Publication history

Received: 24 August 2022
Revised: 03 October 2022
Accepted: 10 October 2022
Published: 07 December 2022
Issue date: April 2023

Copyright

© Tsinghua University Press 2022

Acknowledgements

Acknowledgements

This work was financially supported by the National Natural Science Foundation of China (Nos. 32071334, 51825302, and 21734002) and Natural Science Foundation of Chongqing (Nos. cstc2021jcyj-cxttX0002 and cstc2019jscx-msxmX0160).

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