Fig. 5: TLR4 ligand NP coatings contribute to pro-inflammatory cytokine induction.

a Upstream network prediction further restricted to 3hrPlas-specific corona biomolecules that induce TLR4/MyD88/NF-kB activation. b Schematic representation of recombinant protein pre-coatings to evaluate potential pro-inflammatory biomolecules. Created in BioRender. Shaw, J. (2025) https://BioRender.com/u64r124. c Pro-inflammatory TNFα secretion of macrophages treated with various pre-coated NP coronas. NP coronas evaluated include hemoglobin (20 mg/mL) coatings (HbHigh_PLGA), fibrinogen normal (2 mg/mL) and high (10 mg/mL) (FbNorm_PLGA, FbHigh_PLGA), 3hrPlas_PLGA spiked with Paquinimod S100A9 inhibitor, along with healthy (Naïve) plasma coatings spiked with hemoglobin or fibrinogen. Data sets are presented as mean ± S.D. (Measurements are from n = 3 biological replicates for all samples, with the exception of Media, Hemoglobin, and HbHigh_PLGA which are n = 6). Significance was calculated using a one-way ANOVA with Tukey’s post-hoc test. *P < 0.05; **P < 0.01; ***P < 0.001, ****P < 0.0001. ns, not significant (P > 0.05). Source data are provided as a Source Data file.