Glutathione-depleting organic metal adjuvants for effective NIR-II photothermal immunotherapy

Although photothermal immunotherapy (PTI) is a compelling strategy for tumor therapy, the development of promising photothermal agents to overcome the insufficient immunogenicity of tumor cells and the poor immune response encountered in PTI is still challenging. Herein, commercial small-molecule-ba...

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Bibliographic Details
Main Authors: Chen, Yun, He, Peiying, Jana, Deblin, Wang, Dongdong, Wang, Menghao, Yu, Peiyuan, Zhu, Wei, Zhao, Yanli
Other Authors: School of Physical and Mathematical Sciences
Format: Article
Language:English
Published: 2022
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Online Access:https://hdl.handle.net/10356/162057
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Institution: Nanyang Technological University
Language: English
Description
Summary:Although photothermal immunotherapy (PTI) is a compelling strategy for tumor therapy, the development of promising photothermal agents to overcome the insufficient immunogenicity of tumor cells and the poor immune response encountered in PTI is still challenging. Herein, commercial small-molecule-based organic metal adjuvants (OMAs) are presented, with second near-infrared photoacoustic and photothermal properties as well as the ability to perturb redox homeostasis to potentiate immunogenicity and immune responsiveness. OMAs, assembled from charge-transfer complexes and characterized by a broad substrate scope, high accessibility, and flexibly tuned optical properties, demonstrate strong phototherapeutic and adjuvant abilities via the depletion of glutathione and cysteine, and subsequently elicit systemic immunity by evoking immunogenic cell death, promoting dendritic cell maturation, and increasing T cell infiltration. Furthermore, programmed cell death protein 1 antibody can be employed to synergize with OMAs to suppress tumor immune evasion and ultimately improve the treatment outcomes. This study unlocks new paradigms to provide a versatile OMA-based scaffold for future practical applications.