Harnessing the power of traceable system C-GAP: homologous-targeting to fire up T-cell immune responses with low-dose irradiation
Abstract While radiotherapy-induced immunogenic cell death (ICD) holds potential for enhancing cancer immunotherapy, the conventional high-dose irradiation often leads to an immunosuppressive microenvironment and systemic toxicity. Therefore, a biomimetic nanoplatform cell membrane coated-nitrogen-d...
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| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-03-01
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| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12951-025-03281-6 |
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| Summary: | Abstract While radiotherapy-induced immunogenic cell death (ICD) holds potential for enhancing cancer immunotherapy, the conventional high-dose irradiation often leads to an immunosuppressive microenvironment and systemic toxicity. Therefore, a biomimetic nanoplatform cell membrane coated-nitrogen-doped graphene quantum dots combined with Au nanoparticles (C-GAP) was developed in this study. Firstly, homologous and traceable targeting features of C-GAP enables tumor-selective accumulation, providing reference for the selection of the timing of radiotherapy. Secondly, radiosensitization by C-GAP with Low-dose irradiation (LDI) amplifies reactive oxygen species (ROS) generation to trigger potent ICD. Thirdly, remarkable immune remodeling induced by C-GAP enhances CD8+ T cell infiltration and effector function. Single-cell RNA sequencing revealed that C-GAP-LDI combination upregulates TNF and CCL signaling pathway expression in tumor-infiltrating CD8+ T cells which potentiates tumor eradication. Our findings present a novel approach for safe and effective radioimmunotherapy, where C-GAP sensitized LDI achieves therapeutic enhancement through precise ICD induction and systemic immune activation. Graphical Abstract |
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| ISSN: | 1477-3155 |