'Lipid nanoparticle used in mRNA vaccine promotes tumor metastasis in mouse model'

"Here, we demonstrate that LNP administration promotes tumor metastasis by inducing a systemic inflammatory response. In mouse models, LNP injection triggered acute neutrophil accumulation in the lungs, driven by the release of mitochondrial DNA (mtDNA) from necrotic muscle cells at the injection site.
In this study, we found that intramuscular LNP injection led to localized muscle cell necrosis, releasing mitochondrial DNA (mtDNA) into the circulation as a damage-associated molecular pattern (DAMP). Circulating mtDNA subsequently activated neutrophils via the TLR9-MyD88 and cGAS-STING pathways [31], [32], leading to their accumulation in the lungs and the formation of pro-metastatic niche through NET formation. Importantly, genetic ablation of key signaling components (Tlr9⁻/⁻, MyD88⁻/⁻, Sting⁻/⁻) abrogated this effect, confirming the causal role of LNP-induced inflammation in metastasis. While previous reports have highlighted the immunostimulatory properties of LNP, our findings suggest that their effects extend beyond conventional vaccine adjuvant, potentially influencing cancer progression. We do not categorize this as a “side effect” but rather as a critical consideration for the design and application of mRNA-LNP therapeutics."

https://www.sciencedirect.com/science/article/abs/pii/S1748013226000666?via%3Dihub

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