Monitoring ROS Responsive Fe3O4-based Nanoparticle Mediated Ferroptosis and Immunotherapy via 129Xe MRI.
Angew Chem Int Ed Engl
; 63(22): e202403771, 2024 05 27.
Article
em En
| MEDLINE
| ID: mdl-38551448
ABSTRACT
The immune checkpoint blockade strategy has improved the survival rate of late-stage lung cancer patients. However, the low immune response rate limits the immunotherapy efficiency. Here, we report a ROS-responsive Fe3O4-based nanoparticle that undergoes charge reversal and disassembly in the tumor microenvironment, enhancing the uptake of Fe3O4 by tumor cells and triggering a more severe ferroptosis. In the tumor microenvironment, the nanoparticle rapidly disassembles and releases the loaded GOx and the immune-activating peptide Tuftsin under overexpressed H2O2. GOx can consume the glucose of tumor cells and generate more H2O2, promoting the disassembly of the nanoparticle and drug release, thereby enhancing the therapeutic effect of ferroptosis. Combined with Tuftsin, it can more effectively reverse the immune-suppressive microenvironment and promote the recruitment of effector T cells in tumor tissues. Ultimately, in combination with α-PD-L1, there is significant inhibition of the growth of lung metastases. Additionally, the hyperpolarized 129Xe method has been used to evaluate the Fe3O4 nanoparticle-mediated immunotherapy, where the ventilation defects in lung metastases have been significantly improved with complete lung structure and function recovered. The ferroptosis-enhanced immunotherapy combined with non-radiation evaluation methodology paves a new way for designing novel theranostic agents for cancer therapy.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Imageamento por Ressonância Magnética
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Espécies Reativas de Oxigênio
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Ferroptose
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Imunoterapia
Limite:
Animals
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Humans
Idioma:
En
Revista:
Angew Chem Int Ed Engl
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Angew. Chem. (Int. ed., Internet)
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Angewandte Chemie (International ed. Internet)
Ano de publicação:
2024
Tipo de documento:
Article