Issue 6, 2023

A mitochondria-localized iridium(iii) photosensitizer for two-photon photodynamic immunotherapy against melanoma

Abstract

Conventional photodynamic therapy mainly causes a therapeutic effect on the primary tumor through the localized generation of reactive oxygen species, while metastatic tumors remain poorly affected. Complementary immunotherapy is effective in eliminating small, non-localized tumors distributed across multiple organs. Here, we report the Ir(III) complex Ir-pbt-Bpa as a highly potent immunogenic cell death inducing photosensitizer for two-photon photodynamic immunotherapy against melanoma. Ir-pbt-Bpa can produce singlet oxygen and superoxide anion radicals upon light irradiation, causing cell death by a combination of ferroptosis and immunogenic cell death. In a mouse model with two physically separated melanoma tumors, although only one of the primary tumors was irradiated, a strong tumor reduction of both tumors was observed. Upon irradiation, Ir-pbt-Bpa not only induced the immune response of CD8+ T cells and the depletion of regulatory T cells, but also caused an increase in the number of the effector memory T cells to achieve long-term anti-tumor immunity.

Graphical abstract: A mitochondria-localized iridium(iii) photosensitizer for two-photon photodynamic immunotherapy against melanoma

Supplementary files

Article information

Article type
Edge Article
Submitted
03 dec 2022
Accepted
12 jan 2023
First published
12 jan 2023
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2023,14, 1461-1471

A mitochondria-localized iridium(III) photosensitizer for two-photon photodynamic immunotherapy against melanoma

L. Wang, J. Karges, F. Wei, L. Xie, Z. Chen, G. Gasser, L. Ji and H. Chao, Chem. Sci., 2023, 14, 1461 DOI: 10.1039/D2SC06675K

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