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Inflammatory disease progression shapes nanoparticle biomolecular corona-mediated immune activation profiles

Author

Listed:
  • Jacob R. Shaw

    (University of Maryland School of Medicine)

  • Nicholas Caprio

    (University of Maryland School of Pharmacy)

  • Nhu Truong

    (University of Maryland School of Pharmacy)

  • Mehari Weldemariam

    (University of Maryland School of Pharmacy)

  • Anh Tran

    (University of Maryland School of Pharmacy)

  • Nageswara Pilli

    (University of Maryland School of Pharmacy)

  • Swarnima Pandey

    (University of Maryland School of Pharmacy)

  • Jace W. Jones

    (University of Maryland School of Pharmacy)

  • Maureen A. Kane

    (University of Maryland School of Pharmacy
    University of Maryland School of Medicine)

  • Ryan M. Pearson

    (University of Maryland School of Medicine
    University of Maryland School of Pharmacy
    University of Maryland School of Medicine)

Abstract

Polymeric nanoparticles (NPs) are promising tools used for immunomodulation and drug delivery in various disease contexts. The interaction between NP surfaces and plasma-resident biomolecules results in the formation of a biomolecular corona, which varies patient-to-patient and as a function of disease state. This study investigates how the progression of acute systemic inflammatory disease influences NP corona compositions and the corresponding effects on innate immune cell interactions, phenotypes, and cytokine responses. NP coronas alter cell associations in a disease-dependent manner, induce differential co-stimulatory and co-inhibitory molecule expression, and influence cytokine release. Integrated multi-omics analysis of proteomics, lipidomics, metabolomics, and cytokine datasets highlight a set of differentially enriched TLR4 ligands that correlate with dynamic NP corona-mediated immune activation. Pharmacological inhibition and genetic knockout studies validate that NP coronas mediate this response through TLR4/MyD88/NF-κB signaling. Our findings illuminate the personalized nature of corona formation under a dynamic inflammatory condition and its impact on NP-mediated immune activation profiles and inflammation, suggesting that disease progression-related alterations in plasma composition can manifest in the corona to cause unintended toxicity and altered therapeutic efficacy.

Suggested Citation

  • Jacob R. Shaw & Nicholas Caprio & Nhu Truong & Mehari Weldemariam & Anh Tran & Nageswara Pilli & Swarnima Pandey & Jace W. Jones & Maureen A. Kane & Ryan M. Pearson, 2025. "Inflammatory disease progression shapes nanoparticle biomolecular corona-mediated immune activation profiles," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56210-4
    DOI: 10.1038/s41467-025-56210-4
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    References listed on IDEAS

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