ArticleJournal of nanobiotechnology2025
Mitochondria-targeting polymer cLipG/CuET activates the cGAS/STING pathway to enhance cholangiocarcinoma immunotherapy.
Article in Journal of nanobiotechnology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- The bidirectional immunoregulatory effects of Traditional Chinese Medicine on the cGAS-STING signaling pathway and their translational prospects.Chinese medicine · 2026Review
- Nanomedicine leverages cuproptosis-mediated cGAS-STING activation to enhance antitumor immunity.Journal of nanobiotechnology · 2026Review
- Epigenetic regulation of cuproptosis in cancer: mechanisms, microenvironment, and therapeutic implications.Frontiers in cell and developmental biology · 2026Review
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Authors and funding
17 authors.
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Abstract
backgroundThe remodeling of extracellular matrix often fails chemotherapeutic agents to fight intrahepatic cholangiocarcinoma (ICC). The cGAS/STING pathway can trigger the innate immune response to obtain better immunotherapeutic outcomes.
resultsA cLipG/CuET nanocomposite was designed and synthesized based on glycyrrhizic acid (GA) and copper diethyldithiocarbamate (CuET). GA can open mitochondrial permeability transition pores (MPTPs), allowing Cu (II) to interrupt mitochondrial function through copper toxicity. By activating the cGAS-STING signaling pathway in macrophages, this mitochondrial-targeting polymer (cLipG/CuET) significantly boosted the production of mitochondrial reactive oxygen species (mtROS), and promoted the escape of damaged mitochondrial DNA (mtDNA) from ICC cells. Consequently, M1 polarization of cancer-associated macrophages enhanced the immune response against ICC. In the mouse model, the intravenous administration of cLipG/CuET transformed the ICC from "cold" into "hot".
conclusionsWith a high biosafety, cLipG/CuET exerted a synergistic effect on the immune checkpoint inhibitor αCTLA-4 against ICC, and their combination provided a new therapeutic strategy.
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