Cancer immunotherapy based on image-guided STING activation by nucleotide nanocomplex-decorated ultrasound microbubbles
| العنوان: | Cancer immunotherapy based on image-guided STING activation by nucleotide nanocomplex-decorated ultrasound microbubbles |
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| المؤلفون: | Xuefeng Li, Sina Khorsandi, Yifan Wang, Julien Santelli, Kristin Huntoon, Nhu Nguyen, Mingming Yang, DaeYong Lee, Yifei Lu, Ruoqi Gao, Betty Y. S. Kim, Caroline de Gracia Lux, Robert F. Mattrey, Wen Jiang, Jacques Lux |
| المصدر: | Nature Nanotechnology. 17:891-899 |
| بيانات النشر: | Springer Science and Business Media LLC, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Microbubbles, Nucleotides, Biomedical Engineering, Antigen-Presenting Cells, Membrane Proteins, Bioengineering, Condensed Matter Physics, Nucleotidyltransferases, Atomic and Molecular Physics, and Optics, Nanostructures, Mice, Neoplasms, Animals, General Materials Science, Immunotherapy, Electrical and Electronic Engineering |
| الوصف: | The cytosolic innate immune sensor cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway is crucial for priming adaptive antitumour immunity through antigen-presenting cells (APCs). Natural agonists, such as cyclic dinucleotides (CDNs), activate the cGAS-STING pathway, but their clinical translation is impeded by poor cytosolic entry and serum stability, low specificity and rapid tissue clearance. Here we developed an ultrasound (US)-guided cancer immunotherapy platform using nanocomplexes composed of 2'3'-cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) electrostatically bound to biocompatible branched cationic biopolymers that are conjugated onto APC-targeting microbubbles (MBs). The nanocomplex-conjugated MBs engaged with APCs and efficiently delivered cGAMP into the cytosol via sonoporation, resulting in activation of cGAS-STING and downstream proinflammatory pathways that efficiently prime antigen-specific T cells. This bridging of innate and adaptive immunity inhibited tumour growth in both localized and metastatic murine cancer models. Our findings demonstrate that targeted local activation of STING in APCs under spatiotemporal US stimulation results in systemic antitumour immunity and improves the therapeutic efficacy of checkpoint blockade, thus paving the way towards novel image-guided strategies for targeted immunotherapy of cancer. |
| تدمد: | 1748-3395 1748-3387 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9cb9f587458461465a57b8dcf2c09718 https://doi.org/10.1038/s41565-022-01134-z |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....9cb9f587458461465a57b8dcf2c09718 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 17483395 17483387 |
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