Issue 22, 2023

An iron-containing ferritin-based nanosensitizer for synergistic ferroptosis/sono-photodynamic cancer therapy

Abstract

Ferroptosis is a newly detected iron-dependent form of regulated cell death. Sono-photodynamic therapy (SPDT) can generate reactive oxygen species (ROS) and induce cell death under light and ultrasound. Due to the complexity of tumor physiology and pathology, single-modality often fails to achieve a satisfactory therapeutic effect. The development of a formulation platform with integration of multiple therapeutic modalities using a simple and convenient method is still a challenge. Here, we report the facile construction of a ferritin-based nanosensitizer FCD by co-encapsulating chlorin e6 (Ce6) and dihydroartemisinin (DHA) in horse spleen ferritin, and was employed for synergistic ferroptosis and SPDT. Ferritin in FCD can release Fe3+ under acidic conditions and Fe3+ can be reduced to Fe2+ in the presence of glutathione (GSH). The Fe2+ can react with hydrogen peroxide (H2O2) to produce harmful hydroxyl radicals. Furthermore, a large amount of ROS can be generated via the reaction of Fe2+ with DHA and by simultaneously irradiation of FCD with both light and ultrasound. More importantly, the depletion of GSH by FCD could decrease glutathione peroxidase 4 (GPX4) and increase lipid peroxidation (LPO) levels, thereby inducing ferroptosis. Therefore, by integrating the advantageous GSH-depletion capacity, ROS generation ability, and ferroptosis induction capability into one single nanosystem, FCD can serve as a promising platform for combined chemo-sono-photodynamic therapy of cancer.

Graphical abstract: An iron-containing ferritin-based nanosensitizer for synergistic ferroptosis/sono-photodynamic cancer therapy

Supplementary files

Article information

Article type
Paper
Submitted
06 Jan 2023
Accepted
03 May 2023
First published
19 May 2023

J. Mater. Chem. B, 2023,11, 4958-4971

An iron-containing ferritin-based nanosensitizer for synergistic ferroptosis/sono-photodynamic cancer therapy

Y. Zheng, J. Zheng, M. Du, Y. Yang, X. Li, H. Chen and Y. Gao, J. Mater. Chem. B, 2023, 11, 4958 DOI: 10.1039/D3TB00029J

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