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Drug delivery

A gut–liver axis governs the fate of drug delivery vectors

Nature Reviews Bioengineering (2026)Cite this article

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In vivo delivery systems, including lipid nanoparticles, polymeric nanocarriers and viral vectors, have become foundational to many therapeutics, powering mRNA vaccines, chemotherapies and genome editing. Yet, only a small fraction of injected particles typically reach target tissues, with the majority rapidly removed by hepatic Kupffer cells. Now, writing in Science, Yucai Wang, Shu Zhu, Wei Jiang and colleagues uncover a previously unrecognized gut microbiota-driven endocrine circuit that maintains Kupffer cell activation, thereby dictating the systemic efficiency of therapies delivered by nanocarriers.

Notably, this effect extends across delivery systems, including liposomes, lipid nanoparticles, polymeric nanoparticles, adeno-associated viruses, adenoviruses and lentiviral vectors. “These findings suggest that systemic clearance of nanoscale delivery systems is not determined solely by material design but is driven by signals originating from the gut microbiota,” explains Wang. Therefore, microbiota depletion can amplify the efficacy of chemotherapy, oncolytic virotherapy, and mRNA- or DNA-based genome editing, achieving 3–15-fold gains in delivery efficiency, depending on the vector.

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References

Original article

  • Wang, Q. et al. Commensal-driven serotonin production modulates in vivo delivery of synthetic and viral vectors. Science 391, eadu7686 (2026)

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  1. Nature Reviews Bioengineering https://www.nature.com/natrevbioeng/

    Sadra Bakhshandeh

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  1. Sadra Bakhshandeh
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Correspondence to Sadra Bakhshandeh.

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Bakhshandeh, S. A gut–liver axis governs the fate of drug delivery vectors. Nat Rev Bioeng (2026). https://doi.org/10.1038/s44222-026-00436-4

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