Research ArticleHEALTH AND MEDICINE

Targeted anti–IL-1β platelet microparticles for cardiac detoxing and repair

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Science Advances  05 Feb 2020:
Vol. 6, no. 6, eaay0589
DOI: 10.1126/sciadv.aay0589
  • Fig. 1 Schematic diagram.

    Schematic illustrating the role of Gevokizumab-armed platelet microparticles as cardiac detoxification and repair agents.

  • Fig. 2 Biodistribution of IL1-PMs in mice with acute MI.

    (A) In vivo fluorescent imaging of MI mice or sham mice at various time intervals after intravenous injection of IL1-PM@Cy5.5 or antibody@Cy5.5. (B) Ex vivo fluorescent imaging of the major organs excised from the treated animals. (C) Quantitative analysis of fluorescent intensity in the organs. Antibody, Gevokizumab; IL1-PM, Gevokizumab-armed platelet microparticles. **P < 0.01 indicates that the IL1-PM@Cy5.5–treated MI group is significantly different from the other groups.

  • Fig. 3 Effects of IL1-PM treatment on inflammatory cytokines.

    (A) Cytokine array analysis of the systemic inflammatory cytokine level changes after 72 hours of treatment. (B) Quantitative summary of cytokine array analysis in (A). (C) Quantitative summary of the concentrations of IL-1β in the heart as detected by ELISA (n = 5). P, platelets; G-CSF, granulocyte colony-stimulating factor; ns, not significant. *P < 0.05, **P < 0.01, ***P < 0.001.

  • Fig. 4 Anti-inflammatory ability of IL1-PMs in heart tissue.

    Western blot results for CD45 (A) and cleaved caspase-1 (B) presence in the plasma 72 hours after surgery (n = 3). (C) Histogram summarizing caspase-1 (YVAD-AMC cleavage) activity normalized to the PBS group (n = 5). (D) Quantification of the number of ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain)–positive inflammasomes. (E) Representative image of the formation of ASC-containing inflammasomes 72 hours after MI. HPF, high-power field; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; SA, sarcomeric actin; DAPI, 4′,6-diamidino-2-phenylindole. Scale bar, 20 mm.

  • Fig. 5 IL1-PM treatment reduces cardiac apoptosis.

    (A) Expression of apoptosis-associated protein (caspase-3) analyzed by Western blot 72 hours after treatment. (B) Caspase-3 activity was evaluated using a fluorometric assay kit (n = 5). (C) TUNEL staining for cardiomyocyte apoptosis in the infarcted heart 3 days after MI. Scale bar, 20 μm. (D) Quantification of cardiomyocyte apoptosis. ***P < 0.001.

  • Fig. 6 IL1-PM treatment attenuates cardiac remodeling.

    (A) Representative Masson’s trichrome staining of myocardial sections 70 days after treatment. Quantitative analyses of (B) viable myocardium and (C) scar size from the Masson’s trichrome images. IL1-PM groups versus other three groups. (D) LVEDV and (E) LVESV measured by echocardiography 4 hours, 28 days, and 70 days after treatment (n = 5). (F) LVEFs and (G) LVFSs measured by echocardiogram at baseline (4 hours after MI), 28 days, and 70 days after treatment (n = 5). *P < 0.05, **P < 0.01, ***P < 0.001.

Supplementary Materials

  • Supplementary material for this article is available at http://advances.sciencemag.org/cgi/content/full/6/6/eaay0589/DC1

    Supplementary Materials and Methods

    Fig. S1. Gevokizumab modification.

    Fig. S2. TEM characterization of IL1-PM.

    Fig. S3. Arming of Gevokizumab onto platelets.

    Fig. S4. Confirming antibody conjugation and detoxification rate.

    Fig. S5. Platelet markers on IL1-PM.

    Fig. S6. Inactivated platelet microparticles can bind to damaged vasculatures.

    Fig. S7. Circulation lifetime of IL1-PM in normal mice.

    Fig. S8. Toxicity of IL1-PM treatment and quantification of IL-1β and IL-6 concentrations in the heart.

    Fig. S9. Inflammatory response after treatments.

  • Supplementary Materials

    This PDF file includes:

    • Supplementary Materials and Methods
    • Fig. S1. Gevokizumab modification.
    • Fig. S2. TEM characterization of IL1-PM.
    • Fig. S3. Arming of Gevokizumab onto platelets.
    • Fig. S4. Confirming antibody conjugation and detoxification rate.
    • Fig. S5. Platelet markers on IL1-PM.
    • Fig. S6. Inactivated platelet microparticles can bind to damaged vasculatures.
    • Fig. S7. Circulation lifetime of IL1-PM in normal mice.
    • Fig. S8. Toxicity of IL1-PM treatment and quantification of IL-1β and IL-6 concentrations in the heart.
    • Fig. S9. Inflammatory response after treatments.

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